121 results on '"Coombs GW"'
Search Results
2. Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.
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Coombs, GW, Yee, NWT, Daley, D, Bennett, CM, Robinson, JO, Stegger, M, Shoby, P, Mowlaboccus, S, Coombs, GW, Yee, NWT, Daley, D, Bennett, CM, Robinson, JO, Stegger, M, Shoby, P, and Mowlaboccus, S
- Abstract
BACKGROUND: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020. OBJECTIVES: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ-positive S. aureus initially classified as penicillin-susceptible by the Vitek® 2 automated microbiology system. RESULTS: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ-positive PSSA were from CC15 and were found to be genetically distant from the blaZ-negative CC15 PSSA. The broth microdilution, Etest® and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ-positive PSSA. CONCLUSIONS: In Australia, PSSA bac
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- 2022
3. Complete Genome Sequence of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 1, SCCmec IV[2B], Isolated in the 1990s from Northern Western Australia
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Gill, SR, Karakatsanis, NM, Mowlaboccus, S, Colombi, E, Pearson, JC, Ramsay, JP, Coombs, GW, Gill, SR, Karakatsanis, NM, Mowlaboccus, S, Colombi, E, Pearson, JC, Ramsay, JP, and Coombs, GW
- Abstract
Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) SCCmec IV[2B] has become one of the most common community-associated MRSA clones in Australia. We report the complete genome sequence of one of the earliest isolated Australian S. aureus ST1-MRSA-IV strains, WBG8287, isolated from an Indigenous Australian patient living in the remote Kimberley region of Western Australia.
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- 2021
4. Complete Genome Sequences of Three of the Earliest Community-Associated Methicillin-Resistant Staphylococcus aureus Strains Isolated in Remote Western Australia
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Gill, SR, Karakatsanis, NM, Colombi, E, Mowlaboccus, S, Pearson, JC, Coombs, GW, Ramsay, JP, Gill, SR, Karakatsanis, NM, Colombi, E, Mowlaboccus, S, Pearson, JC, Coombs, GW, and Ramsay, JP
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Initially reported in Western Australia in the 1980s, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major cause of S. aureus infections globally. We report the complete genome sequences of three of the earliest CA-MRSA strains isolated from remote Australian Indigenous communities in the Kimberley region of Western Australia.
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- 2021
5. Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent
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Planet, PJ, Torres, VJ, Steinig, EJ, Duchene, S, Robinson, DA, Monecke, S, Yokoyama, M, Laabei, M, Slickers, P, Andersson, P, Williamson, D, Kearns, A, Goering, RV, Dickson, E, Ehricht, R, Ip, M, O'Sullivan, MVN, Coombs, GW, Petersen, A, Brennan, G, Shore, AC, Coleman, DC, Pantosti, A, de Lencastre, H, Westh, H, Kobayashi, N, Heffernan, H, Strommenger, B, Layer, F, Weber, S, Aamot, HV, Skakni, L, Peacock, SJ, Sarovich, D, Harris, S, Parkhill, J, Massey, RC, Holden, MTG, Bentley, SD, Tong, SYC, Planet, PJ, Torres, VJ, Steinig, EJ, Duchene, S, Robinson, DA, Monecke, S, Yokoyama, M, Laabei, M, Slickers, P, Andersson, P, Williamson, D, Kearns, A, Goering, RV, Dickson, E, Ehricht, R, Ip, M, O'Sullivan, MVN, Coombs, GW, Petersen, A, Brennan, G, Shore, AC, Coleman, DC, Pantosti, A, de Lencastre, H, Westh, H, Kobayashi, N, Heffernan, H, Strommenger, B, Layer, F, Weber, S, Aamot, HV, Skakni, L, Peacock, SJ, Sarovich, D, Harris, S, Parkhill, J, Massey, RC, Holden, MTG, Bentley, SD, and Tong, SYC
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The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated
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- 2019
6. Clonal diversity and geographic distribution of methicillin-resistant Staphylococcus pseudintermedius from Australian animals: Discovery of novel sequence types
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Worthing, KA, Abraham, S, Coombs, GW, Pang, S, Saputra, S, Jordan, D, Trott, DJ, Norris, JM, Worthing, KA, Abraham, S, Coombs, GW, Pang, S, Saputra, S, Jordan, D, Trott, DJ, and Norris, JM
- Abstract
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an increasingly prevalent pathogen in veterinary medicine. This study examined the molecular epidemiology of clinical MRSP isolated from Australian animals. Clinical staphylococci submitted to all Australian veterinary diagnostic laboratories were collected during 2013 and identified using traditional phenotypic tests and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Phenotypic antimicrobial resistance was determined using broth microdilution and disk diffusion. MRSP isolates were characterized by whole genome sequencing which included identification of the mecA gene. Phylogenetic relationships were inferred by comparison of single nucleotide polymorphisms. Of the 669 S. pseudintermedius isolates collected from dogs, cats and cattle, 77 (11.5%) were MRSP. Nineteen multilocus sequence types (STs) were identified, with most isolates belonging to one of five STs (ST71, ST497, ST316, ST496 and ST45). Phylogenetic analysis revealed that Australian ST71 appears closely related to ST71 from overseas. ST497 and ST496 represented novel sequence types, not previously reported outside Australia. Most other STs were novel and only distantly related to each other. Geographical clustering of STs was observed. All isolates belonging to the five main STs were multi- to extensively- drug resistant while isolates from singleton STs generally had lower levels of antimicrobial resistance. The frequency of ciprofloxacin, trimethoprim-sulfamethoxazole, gentamicin, chloramphenicol and tetracycline resistance varied significantly between STs (p<0.01). Australian MRSP isolates are phylogenetically diverse, with a mix of previously unreported and well known international MRSP clones that demonstrate geographic clustering and exhibit both multidrug-resistant and extensively drug-resistant phenotypes.
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- 2018
7. Vancomycin-resistant Enterococcus faecium sequence type 796-rapid international dissemination of a new epidemic clone
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Mahony, AA, Buultjens, AH, Ballard, SA, Grabsch, EA, Xie, S, Seemann, T, Stuart, RL, Kotsanas, D, Cheng, A, Heffernan, H, Roberts, SA, Coombs, GW, Bak, N, Ferguson, JK, Carter, GC, Howden, BP, Stinear, TP, Johnson, PDR, Mahony, AA, Buultjens, AH, Ballard, SA, Grabsch, EA, Xie, S, Seemann, T, Stuart, RL, Kotsanas, D, Cheng, A, Heffernan, H, Roberts, SA, Coombs, GW, Bak, N, Ferguson, JK, Carter, GC, Howden, BP, Stinear, TP, and Johnson, PDR
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BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. METHODS: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. RESULTS: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. CONCLUSIONS: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.
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- 2018
8. Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia
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van Hal, SJ, Steinig, EJ, Andersson, P, Holden, MTG, Harris, SR, Nimmo, GR, Williamson, DA, Heffernan, H, Ritchie, SR, Kearns, AM, Ellington, MJ, Dickson, E, De Lencastre, H, Coombs, GW, Bentley, SD, Parkhill, J, Holt, DC, Giffard, PM, Tong, SYC, van Hal, SJ, Steinig, EJ, Andersson, P, Holden, MTG, Harris, SR, Nimmo, GR, Williamson, DA, Heffernan, H, Ritchie, SR, Kearns, AM, Ellington, MJ, Dickson, E, De Lencastre, H, Coombs, GW, Bentley, SD, Parkhill, J, Holt, DC, Giffard, PM, and Tong, SYC
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Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens.
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- 2018
9. Clonal expansion of new penicillin-resistant clade of serogroup W, clonal complex 11 Neisseria meningitidis, Western Australia
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Mowlaboccus, S, Jolley, KA, Bray, JE, Pang, S, Thin Lee, Y, Bew, JD, Speers, DJ, Keil, AD, Coombs, GW, and Kahler, CM
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In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.
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- 2017
10. Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium
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Buultjens, AH, Lam, MMC, Ballard, S, Monk, IR, Mahony, AA, Grabsch, EA, Grayson, ML, Pang, S, Coombs, GW, Robinson, JO, Seemann, T, Johnson, PDR, Howden, BP, Stinear, TP, Buultjens, AH, Lam, MMC, Ballard, S, Monk, IR, Mahony, AA, Grabsch, EA, Grayson, ML, Pang, S, Coombs, GW, Robinson, JO, Seemann, T, Johnson, PDR, Howden, BP, and Stinear, TP
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From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments.
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- 2017
11. Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin- resistant Staphylococcus aureus: Blurring of the traditional definitions
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Lindsay, J, Bal, AM, Coombs, GW, Holden, MTG, Nimmo, GR, Tattevin, P, and Skov, RL
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biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses - Abstract
The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification.
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- 2016
12. Isolation of mecC MRSA in Australia
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Worthing, KA, Coombs, GW, Pang, S, Abraham, S, Saputra, S, Trott, DJ, Jordan, D, Wong, HS, Abraham, RJ, Norris, JM, Worthing, KA, Coombs, GW, Pang, S, Abraham, S, Saputra, S, Trott, DJ, Jordan, D, Wong, HS, Abraham, RJ, and Norris, JM
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- 2016
13. A Prescription for Resistance: Management of Staphylococcal Skin Abscesses by General Practitioners in Australia
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Parrott, C, Wood, G, Bogatyreva, E, Coombs, GW, Johnson, PDR, Bennett, CM, Parrott, C, Wood, G, Bogatyreva, E, Coombs, GW, Johnson, PDR, and Bennett, CM
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OBJECTIVES: We investigated the management of staphylococcal abscesses (boils) by general practitioners (GPs) in the context of rising antibiotic resistance in community strains of Staphylococcus aureus. DESIGN, SETTING, PARTICIPANTS: We analyzed patient-reported management of 66 cases of uncomplicated skin abscesses from the frequency matched methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) Community-Onset Staphylococcus aureus Household Cohort (COSAHC) study (Melbourne, Australia, 2008-2012). Susceptibilities in all cases were known: 50/66 abscesses were caused by MRSA. In order to investigate GP-reported management of staphylococcal abscesses, we surveyed a random subset of GPs, from the COSAHC study (41), and of GPs (39) who used the same community-based pathology service (December 2011-May 2012). MAIN OUTCOME MEASURES: Patient outcomes, antibiotics prescribed, antibiotic resistance profiles of infecting strains, rates of incision and drainage (I&D), and attitudes to ordering microbiological cultures. RESULTS: MRSA was three times more likely to be cultured from an abscess than MSSA. Patient-reported management revealed 100% were prescribed antibiotics and only 60.6% had I&D. Of those 85% who remembered their prescription(s), 81% of MRSA cases and 23% of MSSA cases initially received inactive antibiotics. Repeat GP visits where antibiotics were changed occurred in 45 MRSA and 7 MSSA cases, although at least 33% of subsequent prescriptions were inactive for the MRSA infections. Patients treated with I&D and antibiotics did no better than those treated with only I&D, regardless of the antibiotic activity. In the GP surveys, 89% reported I&D, with or without antibiotics, to be their preferred management. Only 29.9% of GPs would routinely swab abscesses. CONCLUSION: The recommended management of uncomplicated Staphylococcus abscesses is I&D without antibiotics to reduce exposure to unnecessary antibiotics. In our study, I&D was perfo
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- 2016
14. Convergent Adaptation in the Dominant Global Hospital Clone ST239 of Methicillin-Resistant Staphylococcus aureus
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Gilligan, P, Fowler, V, Baines, SL, Holt, KE, Schultz, MB, Seemann, T, Howden, BO, Jensen, SO, van Hal, SJ, Coombs, GW, Firth, N, Powell, DR, Stinear, TP, Howden, BP, Gilligan, P, Fowler, V, Baines, SL, Holt, KE, Schultz, MB, Seemann, T, Howden, BO, Jensen, SO, van Hal, SJ, Coombs, GW, Firth, N, Powell, DR, Stinear, TP, and Howden, BP
- Abstract
UNLABELLED: Infections caused by highly successful clones of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, including walKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally. IMPORTANCE: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for innumerable drug-re
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- 2015
15. Australian Enterococcal Sepsis Outcome Programme, 2011
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Coombs,GW, Pearson,JC, Le,T, Daly,DA, Robinson,JO, Gottlieb,T, Howden,BP, Johnson,PD, Bennett,CM, Stinear,TP, Turnidge,JD, Coombs,GW, Pearson,JC, Le,T, Daly,DA, Robinson,JO, Gottlieb,T, Howden,BP, Johnson,PD, Bennett,CM, Stinear,TP, and Turnidge,JD
- Abstract
From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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- 2014
16. Molecular epidemiology of enterococcal bacteremia in Australia
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Coombs, GW, Pearson, JC, Dale, DA, Le, T, Robinson, OJ, Gottlieb, T, Howden, BP, Johnson, PD, Bennett, CM, Stinear, TP, Turnidge, JD, Coombs, GW, Pearson, JC, Dale, DA, Le, T, Robinson, OJ, Gottlieb, T, Howden, BP, Johnson, PD, Bennett, CM, Stinear, TP, and Turnidge, JD
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- 2014
17. Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in New Zealand: Rapid Emergence of Sequence Type 5 (ST5)-SCCmec-IV as the Dominant Community-Associated MRSA Clone
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de Lencastre, H, Williamson, DA, Roberts, SA, Ritchie, SR, Coombs, GW, Fraser, JD, Heffernan, H, de Lencastre, H, Williamson, DA, Roberts, SA, Ritchie, SR, Coombs, GW, Fraser, JD, and Heffernan, H
- Abstract
The predominant community-associated MRSA strains vary between geographic settings, with ST8-IV USA300 being the commonest clone in North America, and the ST30-IV Southwest Pacific clone established as the dominant clone in New Zealand for the past two decades. Moreover, distinct epidemiological risk factors have been described for colonisation and/or infection with CA-MRSA strains, although these associations have not previously been characterized in New Zealand. Based on data from the annual New Zealand MRSA survey, we sought to describe the clinical and molecular epidemiology of MRSA in New Zealand. All non-duplicate clinical MRSA isolates from New Zealand diagnostic laboratories collected as part of the annual MRSA survey were included. Demographic data was collected for all patients, including age, gender, ethnicity, social deprivation index and hospitalization history. MRSA was isolated from clinical specimens from 3,323 patients during the 2005 to 2011 annual surveys. There were marked ethnic differences, with MRSA isolation rates significantly higher in Māori and Pacific Peoples. Over the study period, there was a significant increase in CA-MRSA, and a previously unidentified PVL-negative ST5-IV spa t002 clone replaced the PVL-positive ST30-IV Southwest Pacific clone as the dominant CA-MRSA clone. Of particular concern was the finding of several successful and virulent MRSA clones from other geographic settings, including ST93-IV (Queensland CA-MRSA), ST8-IV (USA300) and ST772-V (Bengal Bay MRSA). Ongoing molecular surveillance is essential to prevent these MRSA strains becoming endemic in the New Zealand healthcare setting.
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- 2013
18. Genomic Insights to Control the Emergence of Vancomycin-Resistant Enterococci
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Parkhill, J, Howden, BP, Holt, KE, Lam, MMC, Seemann, T, Ballard, S, Coombs, GW, Tong, SYC, Grayson, ML, Johnson, PDR, Stinear, TP, Parkhill, J, Howden, BP, Holt, KE, Lam, MMC, Seemann, T, Ballard, S, Coombs, GW, Tong, SYC, Grayson, ML, Johnson, PDR, and Stinear, TP
- Abstract
UNLABELLED: Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm. IMPORTANCE: Enterococcus faecium is an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in ho
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- 2013
19. Genetic diversity among community methicillin-resistant Staphylococcus aureus strains causing outpatient infections in Australia
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Coombs, GW, Nimmo, GR, Bell, JM, Huygens, F, O'Brien, FG, Malkowski, MJ, Pearson, JC, Stephens, AJ, Giffard, Philip Morrison, Australian Group for Antimicrobial Resistance, Coombs, GW, Nimmo, GR, Bell, JM, Huygens, F, O'Brien, FG, Malkowski, MJ, Pearson, JC, Stephens, AJ, Giffard, Philip Morrison, and Australian Group for Antimicrobial Resistance
- Abstract
Increasing reports of the appearance of novel nonmultiresistant methicillin-resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the spread of hospital MRSA strains into the community are cause for public health concern. We conducted two national surveys of unique isolates of S. aureus from clinical specimens collected from nonhospitalized patients commencing in 2000 and 2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of 2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were nonmultiresistant (resistant to less than three of nine antibiotics) in both surveys. The majority of multiresistant MRSA isolates in both surveys belonged to two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the 11 AUS-3 isolates selected for multilocus sequence typing (MLST) and staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III (where ST is the sequence type) and thus belonged to the same clone as the eastern Australian MRSA strain of the 1980s, which spread internationally. Four predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST, and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1), ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three clones are associated with community acquisition. A total of 14 STs were identified in the surveys, including six unique clones of novel nonmultiresistant MRSA, namely, STs 73, 93, 129, 75, and 80slv and a new ST. SCCmec types IV and V were present in diverse genetic backgrounds. These findings provide support for the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm that both hospital and community strains of MRSA are now common in nonhospitalized patients throughout Australia.
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- 2004
20. Antibiotic Choice May Not Explain Poorer Outcomes in Patients With Staphylococcus aureus Bacteremia and High Vancomycin Minimum Inhibitory Concentrations.
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Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, Anderson TL, Roberts SA, Gao W, Christiansen KJ, Coombs GW, Johnson PD, and Howden BP
- Abstract
(See the editorial commentary by Holland and Fowler Jr, on pages 329-31.) Background. There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. Methods. We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. Results. We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 [mu]g/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not. Conclusions. We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome. [ABSTRACT FROM AUTHOR]
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- 2011
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21. Intrafamilial transmission of methicillin-resistant Staphylococcus aureus.
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Pozzi LS, Robinson JO, Pearson JC, Christiansen KJ, Coombs GW, Murray RJ, Pozzi Langhi, Sabrina A, Robinson, James O, Pearson, Julie C, Christiansen, Keryn J, Coombs, Geoffrey W, and Murray, Ronan J
- Published
- 2009
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22. Emergence and clonal expansion of a qacA-harbouring sequence type 45 lineage of methicillin-resistant Staphylococcus aureus.
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Nong Y, Steinig E, Pollock GL, Taiaroa G, Carter GP, Monk IR, Pang S, Daley DA, Coombs GW, Forde BM, Harris PNA, Sherry NL, Howden BP, Pasricha S, Baines SL, and Williamson DA
- Subjects
- Humans, Staphylococcus aureus genetics, Bayes Theorem, Phylogeny, Membrane Transport Proteins genetics, Bacterial Proteins genetics, Australia, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
The past decade has seen an increase in the prevalence of sequence type (ST) 45 methicillin-resistant Staphylococcus aureus (MRSA), yet the underlying drivers for its emergence and spread remain unclear. To better understand the worldwide dissemination of ST45 S. aureus, we performed phylogenetic analyses of Australian isolates, supplemented with a global population of ST45 S. aureus genomes. Our analyses revealed a distinct lineage of multidrug-resistant ST45 MRSA harbouring qacA, predominantly found in Australia and Singapore. Bayesian inference predicted that the acquisition of qacA occurred in the late 1990s. qacA was integrated into a structurally variable region of the chromosome containing Tn552 (carrying blaZ) and Tn4001 (carrying aac(6')-aph(2")) transposable elements. Using mutagenesis and in vitro assays, we provide phenotypic evidence that qacA confers tolerance to chlorhexidine. These findings collectively suggest both antimicrobial resistance and the carriage of qacA may play a role in the successful establishment of ST45 MRSA., (© 2024. The Author(s).)
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- 2024
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23. Corrigendum: Genomic characterisation of a unique Panton-Valentine leucocidin-positive community-associated methicillin-resistant Staphylococcus aureus lineage increasingly impacting Australian indigenous communities.
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Ramsay JP, Parahitiyawa N, Mowlaboccus S, Mullally CA, Yee NWT, Shoby P, Colombi E, Tan HL, Pearson JC, and Coombs GW
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- 2024
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24. Genomic characterization of a unique Panton-Valentine leucocidin-positive community-associated methicillin-resistant Staphylococcus aureus lineage increasingly impacting on Australian indigenous communities.
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Ramsay JP, Parahitiyawa N, Mowlaboccus S, Mullally CA, Yee NWT, Shoby P, Colombi E, Tan HL, Pearson JC, and Coombs GW
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- Australia, Leukocidins genetics, Genomics, Western Australia, Methicillin-Resistant Staphylococcus aureus genetics
- Abstract
In 2010 a single isolate of a trimethoprim-resistant multilocus sequence type 5, Panton-Valentine leucocidin-positive, community-associated methicillin-resistant Staphylococcus aureus (PVL-positive ST5 CA-MRSA), colloquially named WA121, was identified in northern Western Australia (WA). WA121 now accounts for ~14 % of all WA MRSA infections. To gain an understanding of the genetic composition and phylogenomic structure of WA121 isolates we sequenced the genomes of 155 WA121 isolates collected 2010-2021 and present a detailed genomic description. WA121 was revealed to be a single clonally expanding lineage clearly distinct from sequenced ST5 strains reported outside Australia. WA121 strains were typified by the presence of the distinct PVL phage φSa2wa-st5, the recently described methicillin resistance element SCC mec IVo carrying the trimethoprim resistance ( dfrG ) transposon Tn 4791 , the novel β-lactamase transposon Tn 7702 and the epidermal cell differentiation inhibitor (EDIN-A) plasmid p2010-15611-2. We present evidence that SCC mec IVo together with Tn 4791 has horizontally transferred to Staphylococcus argenteus and evidence of intragenomic movement of both Tn 4791 and Tn 7702 . We experimentally demonstrate that p2010-15611-2 is capable of horizontal transfer by conjugative mobilization from one of several WA121 isolates also harbouring a pWBG749-like conjugative plasmid. In summary, WA121 is a distinct and clonally expanding Australian PVL-positive CA-MRSA lineage that is increasingly responsible for infections in indigenous communities in northern and western Australia. WA121 harbours a unique complement of mobile genetic elements and is capable of transferring antimicrobial resistance and virulence determinants to other staphylococci.
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- 2023
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25. Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.
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Gordon JP, Al Taie A, Miller RL, Dennis JW, Blaskovich MAT, Iredell JR, Turnidge JD, Coombs GW, Grolman DC, and Youssef J
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Introduction: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making., Methods: A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied., Results: Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million., Discussion: Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here., Conclusion: These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials., (© 2023. The Author(s).)
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- 2023
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26. Mycoplasma and Ureaplasma Donor-Derived Infection and Hyperammonemia Syndrome in 4 Solid Organ Transplant Recipients From a Single Donor.
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Wigston C, Lavender M, Long R, Sankhesara D, Ching D, Weaire-Buchanan G, Mowlaboccus S, Coombs GW, Lam K, Wrobel J, Yaw MC, Musk M, and Boan P
- Abstract
Hyperammonemia syndrome (HS) is a life-threatening condition occurring in solid organ transplant patients, affecting primarily lung recipients, and is associated with Mycoplasma hominis and/or Ureaplasma spp infection. The organ donor was a young man who died of hypoxic brain injury and had urethral discharge antemortem. The donor and 4 solid organ transplant recipients had infection with M hominis and/or Ureaplasma spp. The lung and heart recipients both developed altered conscious state and HS associated with M hominis and Ureaplasma spp infections. Despite treatment with antibiotics and ammonia scavengers, both the lung and heart recipients died at day +102 and day +254, respectively. After diagnosis in the thoracic recipients, screening samples from the liver recipient and 1 kidney recipient were culture positive for M hominis with or without Ureaplasma spp. Neither the liver nor kidney recipients developed HS. Our case series demonstrates the unique finding of M hominis and Ureaplasma spp dissemination from an immunocompetent donor across 4 different organ recipients. Phylogenetic whole genome sequencing analysis demonstrated that M hominis samples from recipients and donor were closely related, suggesting donor-derived infection. Screening of lung donors and/or recipients for Mycoplasma and Ureaplasma spp is recommended, as well as prompt treatment with antimicrobials to prevent morbidity., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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27. Travel-associated lineages and unique endemic antimicrobial-susceptible lineages of Neisseria gonorrhoeae predominate in Western Australia.
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Al Suwayyid BA, Haese EC, Mowlaboccus S, Pearson JC, Whiley DM, Armstrong PK, Giele CM, Mak DB, Bastian L, Wise MJ, Coombs GW, and Kahler CM
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- Humans, Neisseria gonorrhoeae, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Azithromycin pharmacology, Multilocus Sequence Typing, Western Australia epidemiology, Bayes Theorem, Travel, Molecular Epidemiology, Gonorrhea epidemiology, Gonorrhea drug therapy, Anti-Infective Agents
- Abstract
In Australia, gonococcal isolates are monitored for antimicrobial susceptibilities. In Western Australia (WA), gonorrhoea notification rates increased by 63 % between 2013 and 2016, with the steepest increase occurring between 2015 and 2016, before stabilizing at this higher baseline between 2017 and 2020. This increased prevalence was associated with antimicrobial-susceptible (AMS) lineages. To understand the provenance of these isolates causing gonorrhoea in WA, whether they were introduced or expanded from endogenous lineages, 741 isolates were collected in 2017 and characterized by both iPLEX typing and whole genome sequencing (WGS). Antibiograms and genocoding of the isolates revealed that AMS isolates were most prevalent in the remote regions, while the urban/rural regions were characterized by antimicrobial-resistant (AMR) isolates. iPLEX typing identified 78 iPLEX genotypes (WA-1 to WA-78) of which 20 accounted for over 88 % of isolates. WA-10 was the most frequently identified genotype in the urban/rural regions whilst WA-29 was the most frequently identified genotype in the remote regions. Genotypes WA-38, WA-52 and WA-13 accounted for 81 % ( n =36/44) of the azithromycin-resistant N. gonorrhoeae (AziR) isolates. A representative isolate of each iPLEX genotype and AMR biotype was whole genome sequenced and analysed using MLST, NG-MAST and NG-STAR, and the novel core genome clustering Ng_cgc_400 typing scheme. Five predominant Bayesian population groups (termed BPG-1 to 5) were identified in the study collection. BPG-1 and BPG-2 were associated with AMS isolates from the remote regions. BPG-1 and BPG-2 were shown to be unique to the remote regions based on a minimum spanning tree against 4000 international isolates. AMS isolates in urban/rural regions were dominated by international lineages. AziR and Cef DS (decreased susceptibility to ceftriaxone) was concentrated in three urban/rural genomic groups (BPG-3, 4 and 5). Azithromycin minimum inhibitory concentrations (0.5-16 mg l
-1 ) correlated with the accumulation of mtrR mutations or/and the fraction of 23S rRNA C2611T mutated copies. The majority of isolates in BPG-3, 4 and 5 could be correlated with known AMR lineages circulating globally and nationally. In conclusion, the surge in AMS isolates in WA in 2017 was due to importation of international AMS lineages into urban/rural regions, whilst the local AMS lineages persisted largely in the remote regions. Bridging between the urban/rural and remote regions was relatively rare, but continued surveillance is required to prevent ingress of AMR strains/lineages into the remote regions of WA.- Published
- 2023
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28. Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.
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Coombs GW, Yee NWT, Daley D, Bennett CM, Robinson JO, Stegger M, Shoby P, and Mowlaboccus S
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Background: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020., Objectives: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ -positive S. aureus initially classified as penicillin-susceptible by the Vitek
® 2 automated microbiology system., Results: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ -positive PSSA were from CC15 and were found to be genetically distant from the blaZ -negative CC15 PSSA. The broth microdilution, Etest® and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ -positive PSSA., Conclusions: In Australia, PSSA bacteremia is not caused by the expansion of a single clone. Approximately 10% of S. aureus classified as penicillin-susceptible by the Vitek® 2 harbored blaZ . Consequently, we recommend that confirmation of Vitek® 2 PSSA be performed using an alternative method, such as disc diffusion with careful interpretation of the zone edge.- Published
- 2022
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29. Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.
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Campbell AJ, Mowlaboccus S, Coombs GW, Daley DA, Al Yazidi LS, Phuong LK, Leung C, Best EJ, Webb RH, Voss L, Athan E, Britton PN, Bryant PA, Butters CT, Carapetis JR, Ching NS, Francis J, Hung TY, Nourse C, Ojaimi S, Tai A, Vasilunas N, McMullan B, Bowen AC, and Blyth CC
- Subjects
- Australia epidemiology, Child, Humans, Molecular Epidemiology, Prospective Studies, Staphylococcus aureus, Whole Genome Sequencing, Bacteremia epidemiology, Bacteremia microbiology, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
- Abstract
Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration., Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort., Results: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2])., Conclusion: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management., Competing Interests: Declaration of Competing Interest P.A.B. reports grants from National Health and Medical Research Council, Medical Research Futures Fund and Murdoch Children's Research Institute outside the submitted work and travel funds from the Royal Children's Hospital. S.O. has acted on an advisory board for CSL-Behring. All remaining authors have no reported conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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30. The changing molecular epidemiology of Enterococcus faecium harbouring the van operon at a teaching hospital in Western Australia: A fifteen-year retrospective study.
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Lee T, Pang S, Daley DA, Pearson JC, Abraham S, and Coombs GW
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- Anti-Bacterial Agents, Hospitals, Teaching, Humans, Microbial Sensitivity Tests, Molecular Epidemiology, Operon, Phylogeny, Retrospective Studies, Western Australia, Enterococcus faecium genetics, Gram-Positive Bacterial Infections
- Abstract
Introduction: Enterococcus faecium is an opportunistic pathogen that has become one of the leading causes of hospital acquired infection that are resistant to multiple critically important antimicrobials., Aim: The objective of the study was to describe the molecular characteristics and relationship between major strains of E. faecium harbouring the van operon and to determine if the strains had increasing virulence and antimicrobial resistance determinants over time., Methods: E. faecium harbouring the van operon detected using PCR from surveillance rectal swabs of patients that were admitted to high-risk units at a Perth teaching hospital from 2001 to 2015 were retrospectively analysed using a whole genome sequencing and bioinformatics approach., Results: ST18, ST78, ST80, ST173, ST203 and ST555 were identified as the major STs accounting for 93.7% of E. faecium isolates. Except for ST173, major STs identified at Royal Perth Hospital (RPH) have been reported across Australia and internationally. Isolates from each ST formed independently branched phylogenetic clusters with each harbouring unique virulence and antimicrobial resistance profiles. Depending on the ST, different genes conferring resistance to similar antimicrobial classes were identified. Except for ST80 which harboured the vanA type operon, all major strains harboured the vanB operon conferring only vancomycin resistance., Conclusion: Major strains of E. faecium isolated over 15-years showed unique virulome and resistome profiles with no indication of increasing virulence or antimicrobial resistance determinants. Strains were distantly related and the acquisition of different genes encoding similar antimicrobial resistances suggest the independent evolution of each strain., Data Summary: The whole genome sequences of all isolates from this study are accessible from the NCBI-SRA database under project number PRJNA575940 and PRJNA524213. Published reference sequence Aus0004 was obtained from NCBI-SRA under project number PRJNA86649 DOI:10.1128/JB.00259-12., (Crown Copyright © 2021. Published by Elsevier GmbH. All rights reserved.)
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- 2022
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31. Complete Genome Sequences of Three of the Earliest Community-Associated Methicillin-Resistant Staphylococcus aureus Strains Isolated in Remote Western Australia.
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Karakatsanis NM, Colombi E, Mowlaboccus S, Pearson JC, Coombs GW, and Ramsay JP
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Initially reported in Western Australia in the 1980s, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major cause of S. aureus infections globally. We report the complete genome sequences of three of the earliest CA-MRSA strains isolated from remote Australian Indigenous communities in the Kimberley region of Western Australia.
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- 2021
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32. Complete Genome Sequence of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 1, SCC mec IV[2B], Isolated in the 1990s from Northern Western Australia.
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Karakatsanis NM, Mowlaboccus S, Colombi E, Pearson JC, Ramsay JP, and Coombs GW
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Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) SCC mec IV[2B] has become one of the most common community-associated MRSA clones in Australia. We report the complete genome sequence of one of the earliest isolated Australian S. aureus ST1-MRSA-IV strains, WBG8287, isolated from an Indigenous Australian patient living in the remote Kimberley region of Western Australia.
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- 2021
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33. Molecular characterization of fosfomycin-resistant Escherichia coli urinary tract infection isolates from Australia.
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Mowlaboccus S, Daley DA, Birdsall J, Gottlieb T, Merlino J, Nimmo GR, George N, Korman T, Streitberg R, Robson J, Peachey G, Collignon P, Bradbury S, Rogers BA, and Coombs GW
- Subjects
- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Australia epidemiology, Humans, Microbial Sensitivity Tests, beta-Lactamases, Drug Resistance, Bacterial, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli Infections drug therapy, Escherichia coli Infections epidemiology, Fosfomycin pharmacology, Urinary Tract Infections drug therapy, Urinary Tract Infections epidemiology
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- 2021
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34. Genome-wide association studies reveal candidate genes associated to bacteraemia caused by ST93-IV CA-MRSA.
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Pang S, Daley DA, Sahibzada S, Mowlaboccus S, Stegger M, and Coombs GW
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- Australia, Genome-Wide Association Study, Humans, Bacteremia, Community-Acquired Infections, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections genetics
- Abstract
Background: The global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to screen for genetic traits that might have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to search for potential virulence genes associated with bacteraemia., Results: Based on single nucleotide polymorphism phylogenetics we revealed two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002-2017) revealed an observed gain in accessory genes amongst the clone's population. GWAS analysis on the bacteraemia isolates identified two gene candidates that have previously been associated to this kind of infection., Conclusions: Although this hypothesis was not tested here, it is possible that the emergence of a ST93-IV clade containing additional virulence genes might be related to the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. More importantly, our data also demonstrated that GWAS can reveal candidate genes for further investigations on the pathogenesis and evolution of MRSA strains within a same lineage.
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- 2021
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35. Antimicrobial Resistance in Porcine Enterococci in Australia and the Ramifications for Human Health.
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Lee T, Jordan D, Sahibzada S, Abraham R, Pang S, Coombs GW, O'Dea M, and Abraham S
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- Animals, Australia, Chickens microbiology, Enterococcus genetics, Enterococcus isolation & purification, Environmental Monitoring, Genome, Bacterial, Humans, Microbial Sensitivity Tests, Sepsis microbiology, Swine, Anti-Bacterial Agents pharmacology, Cecum microbiology, Drug Resistance, Bacterial genetics, Enterococcus drug effects
- Abstract
Enterococci are ubiquitous opportunistic pathogens that have become a major public health issue globally. The increasing prevalence of antimicrobial resistance in hospital-adapted enterococci had been thought to originate from livestock. However, this association between livestock and hospital-adapted enterococci is currently unclear. This study investigates the antimicrobial susceptibilities of enterococci isolated from pig cecal samples and compares the genomic characteristics of Enterococcus faecium from pigs to those of isolates from meat chickens and from human sepsis cases. From 200 cecal samples, antimicrobial susceptibility testing was performed for E. faecium ( n = 84), E. hirae ( n = 36), and E. faecalis ( n = 17). Whole-genome sequencing was performed for all E. faecium isolates, and the sequences were compared to those of previously studied isolates from meat chickens and human sepsis cases through bioinformatics analysis. Resistance (non-wild type) to erythromycin, gentamicin, tetracycline, ampicillin, daptomycin, virginiamycin, and quinupristin-dalfopristin was identified. More importantly, except for a single isolate harboring the vanC operon, no resistance was observed in the three species to vancomycin, teicoplanin, and linezolid, which are critically important antimicrobials used to treat enterococcal infections in humans. The E. faecium isolates from chickens were genetically distinct from human and pig isolates, which were more closely related. Human strains that were closely related to pig strains were not typical "hospital-adapted strains" as previously identified. The results of this study show that enterococci from Australian finisher pigs are not a source of resistance to critically important antimicrobials and that E. faecium from pigs is not part of the current human hospital-adapted population. IMPORTANCE Resistance to the critically important antimicrobials vancomycin, teicoplanin, and linezolid is not found in enterococci collected from Australian finisher pigs. However, some antimicrobial resistance was observed. In particular, resistance to quinupristin-dalfopristin, a combination of two streptogramin class antimicrobials, was identified despite the absence of streptogramin use Australia-wide since 2005. Other observed resistance among enterococci from pigs include chloramphenicol, erythromycin, and tetracycline resistance. Genomic comparison of E. faecium from Australian pigs to isolates collected from previous studies on chickens and humans indicate that E. faecium from pigs are genetically more similar to those of humans than those from chickens. Despite the increased genetic similarities, E. faecium strains from pigs are phylogenetically distinct and did not belong to the dominant sequence types found in hospital-adapted strains causing sepsis in humans. Therefore, the results indicate that Australian finisher pigs are not a source of hospital-adapted E. faecium in Australia., (Copyright © 2021 American Society for Microbiology.)
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- 2021
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36. Global Epidemiology and Evolutionary History of Staphylococcus aureus ST45.
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Effelsberg N, Stegger M, Peitzmann L, Altinok O, Coombs GW, Pichon B, Kearns A, Randad PR, Heaney CD, Bletz S, Schaumburg F, and Mellmann A
- Subjects
- Australia epidemiology, Bayes Theorem, Europe epidemiology, Humans, Phylogeny, Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
Staphylococcus aureus ST45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. It is one of the most prevalent carrier lineages but also frequently causes severe invasive disease, such as bacteremia. Little is known about its evolutionary history. In this study, we used whole-genome sequencing to analyze a large collection of 451 diverse ST45 isolates from 6 continents and 26 countries. De novo -assembled genomes were used to understand genomic plasticity and to perform coalescent analyses. The ST45 population contained two distinct sublineages, which correlated with the isolates' geographical origins. One sublineage primarily consisted of European/North American isolates, while the second sublineage primarily consisted of African and Australian isolates. Bayesian analysis predicted ST45 originated in northwestern Europe about 500 years ago. Isolation time, host, and clinical symptoms did not correlate with phylogenetic groups. Our phylogenetic analyses suggest multiple acquisitions of the SCC mec element and key virulence factors throughout the evolution of the ST45 lineage., (Copyright © 2020 American Society for Microbiology.)
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- 2020
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37. Investigation of a Lomentospora prolificans case cluster with whole genome sequencing.
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Boan P, Pang S, Gardam DJ, Darragh H, Wright M, and Coombs GW
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Lomentospora prolificans has caused outbreaks in immunocompromised patients. We performed whole genome sequencing (WGS) on 4 L. prolificans isolates from infections occurring during an 8-month period in the haematology unit at Hospital 1., and 2 isolates from unrelated infections at Hospital 2., showing a high number of mutational differences (>10,000 single nucleotide polymorphisms) between L. prolificans isolates from Hospital 1. Novel typing of isolates by WGS did not demonstrate a single causative strain., Competing Interests: There are none, (© 2020 The Authors.)
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- 2020
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38. Marked increase in community-associated methicillin-resistant Staphylococcus aureus infections, Western Australia, 2004-2018.
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Bloomfield LE, Coombs GW, Tempone S, and Armstrong PK
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- Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Toxins genetics, Bacterial Toxins metabolism, Child, Child, Preschool, Community-Acquired Infections epidemiology, Exotoxins genetics, Exotoxins metabolism, Female, Genotype, Humans, Incidence, Infant, Leukocidins genetics, Leukocidins metabolism, Male, Methicillin-Resistant Staphylococcus aureus classification, Middle Aged, Retrospective Studies, Risk Factors, Western Australia epidemiology, Young Adult, Community-Acquired Infections microbiology, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
- Abstract
This study presents enhanced surveillance data from 2004 to 2018 for all community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) specimens collected in Western Australia (WA), and describes the changing epidemiology over this period. A total of 57 557 cases were reviewed. Annual incidence rates increased from 86.2 cases per 100 000 population to 245.6 per 100 000 population (IRR = 2.9, CI95 2.7-3.0). The proportion of isolates carrying Panton-Valentine leucocidin (PVL)-associated genes increased from 3.4% to 59.8% (χ2 test for trend 7021.9, P < 0.001). The emergence of PVL-positive, 'Queensland CA-MRSA' (ST93-IV) and 'WA 121' (ST5-IV) accounted for the majority of increases in CA-MRSA across the study period. It is unclear why some clones are more prolific in certain regions. In WA, CA-MRSA rates increase as indices of temperature and humidity increase after controlling for socioeconomic disadvantage. We suggest climatic conditions may contribute to transmission, along with other socio-behavioural factors. A better understanding of the ability for certain clones to form ecological niches and cause outbreaks is required.
- Published
- 2020
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39. Diversity of bacteriophages encoding Panton-Valentine leukocidin in temporally and geographically related Staphylococcus aureus.
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Coombs GW, Baines SL, Howden BP, Swenson KM, and O'Brien FG
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- Cell Lineage, DNA, Bacterial genetics, Genotype, Geography, Lysogeny, Methicillin-Resistant Staphylococcus aureus genetics, Molecular Epidemiology, Multilocus Sequence Typing, Open Reading Frames, Prophages genetics, Virulence Factors genetics, Western Australia, Bacterial Toxins genetics, Bacteriophages genetics, Exotoxins genetics, Leukocidins genetics, Methicillin-Resistant Staphylococcus aureus virology
- Abstract
Production of the Panton-Valentine leukocidin (PVL) by Staphylococcus aureus is mediated via the genes lukS-PV and lukF-PV which are carried on bacteriophage ϕSa2. PVL is associated with S. aureus strains that cause serious infections and clones of community-associated methicillin-resistant S. aureus (CA-MRSA) that have additionally disseminated widely. In Western Australia (WA) the original CA-MRSA were PVL negative however, between 2005 and 2008, following the introduction of eight international PVL-positive CA-MRSA, PVL-positive WA CA-MRSA were found. There was concern that PVL bacteriophages from the international clones were transferring into the local clones, therefore a comparative study of PVL-carrying ϕSa2 prophage genomes from historic WA PVL-positive S. aureus and representatives of all PVL-positive CA-MRSA isolated in WA between 2005 and 2008 was performed. The prophages were classified into two genera and three PVL bacteriophage groups and had undergone many recombination events during their evolution. Comparative analysis of mosaic regions of selected bacteriophages using the Alignments of bacteriophage genomes (Alpha) aligner revealed novel recombinations and modules. There was heterogeneity in the chromosomal integration sites, the lysogeny regulation regions, the defence and DNA processing modules, the structural and packaging modules and the lukSF-PV genes. One WA CA-MRSA (WA518751) and one international clone (Korean Clone) have probably acquired PVL-carrying ϕSa2 in WA, however these clones did not disseminate in the community. Genetic heterogeneity made it impossible to trace the source of the PVL prophages in the other WA clones. Against this background of PVL prophage diversity, the sequence of one group, the ϕSa2USA/ϕSa2wa-st93 group, was remarkably stable over at least 20 years and associated with the highly virulent USA300 and ST93-IVa CA-MRSA lineages that have disseminated globally., Competing Interests: The authors declared that no competing interests exist.
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- 2020
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40. Meningococcal Disease-Associated Prophage-Like Elements Are Present in Neisseria gonorrhoeae and Some Commensal Neisseria Species.
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Al Suwayyid BA, Rankine-Wilson L, Speers DJ, Wise MJ, Coombs GW, and Kahler CM
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- Gene Transfer, Horizontal genetics, Gene Transfer, Horizontal physiology, Inovirus genetics, Neisseria cinerea virology, Neisseria gonorrhoeae virology, Neisseria lactamica virology, Phylogeny, Meningococcal Infections virology, Neisseria virology, Prophages genetics
- Abstract
Neisseria spp. possess four genogroups of filamentous prophages, termed Nf1 to 4. A filamentous bacteriophage from the Nf1 genogroup termed meningococcal disease-associated phage (MDA φ) is associated with clonal complexes of Neisseria meningitidis that cause invasive meningococcal disease. Recently, we recovered an isolate of Neisseria gonorrhoeae (ExNg63) from a rare case of gonococcal meningitis, and found that it possessed a region with 90% similarity to Nf1 prophages, specifically, the meningococcal MDA φ. This led to the hypothesis that the Nf1 prophage may be more widely distributed amongst the genus Neisseria. An analysis of 92 reference genomes revealed the presence of intact Nf1 prophages in the commensal species, Neisseria lactamica and Neisseria cinerea in addition to the pathogen N. gonorrhoeae. In N. gonorrhoeae, Nf1 prophages had a restricted distribution but were present in all representatives of MLST ST1918. Of the 160 phage integration sites identified, only one common insertion site was found between one isolate of N. gonorrhoeae and N. meningitidis. There was an absence of any obvious conservation of the receptor for prophage entry, PilE, suggesting that the phage may have been obtained by natural transformation. An examination of the restriction modification systems and mutated mismatch repair systems with prophage presence suggested that there was no obvious preference for these hosts. A timed phylogeny inferred that N. meningitidis was the donor of the Nf1 prophages in N. lactamica and N. gonorrhoeae. Further work is required to determine whether Nf1 prophages are active and can act as accessory colonization factors in these species., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2020
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41. Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.
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Steinig EJ, Duchene S, Robinson DA, Monecke S, Yokoyama M, Laabei M, Slickers P, Andersson P, Williamson D, Kearns A, Goering RV, Dickson E, Ehricht R, Ip M, O'Sullivan MVN, Coombs GW, Petersen A, Brennan G, Shore AC, Coleman DC, Pantosti A, de Lencastre H, Westh H, Kobayashi N, Heffernan H, Strommenger B, Layer F, Weber S, Aamot HV, Skakni L, Peacock SJ, Sarovich D, Harris S, Parkhill J, Massey RC, Holden MTG, Bentley SD, and Tong SYC
- Subjects
- Anti-Bacterial Agents pharmacology, Asia epidemiology, Community-Acquired Infections epidemiology, Community-Acquired Infections transmission, Evolution, Molecular, Genome, Bacterial, Humans, India, Methicillin-Resistant Staphylococcus aureus classification, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus isolation & purification, Phylogeny, Staphylococcal Infections epidemiology, Staphylococcal Infections transmission, Staphylococcus aureus classification, Staphylococcus aureus drug effects, Staphylococcus aureus genetics, Community-Acquired Infections microbiology, Drug Resistance, Multiple, Bacterial, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification
- Abstract
The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere. IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world., (Copyright © 2019 Steinig et al.)
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- 2019
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42. Evolution of a 72-Kilobase Cointegrant, Conjugative Multiresistance Plasmid in Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from the Early 1990s.
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Yui Eto K, Firth N, Davis AM, Kwong SM, Krysiak M, Lee YT, O'Brien FG, Grubb WB, Coombs GW, Bond CS, and Ramsay JP
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- Community-Acquired Infections epidemiology, Community-Acquired Infections microbiology, Drug Resistance, Multiple, Bacterial genetics, Genes, Bacterial genetics, Humans, Sequence Alignment, Sequence Analysis, DNA, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology, Western Australia epidemiology, Methicillin-Resistant Staphylococcus aureus genetics, Plasmids genetics
- Abstract
Horizontal transfer of plasmids encoding antimicrobial resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s, the first CA-MRSA strain isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline, and penicillin resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA; however, fusidic acid resistance plasmids related to pWBG753 were also present in the first European CA-MRSA isolates at the time. Here, we characterize a 72-kb conjugative plasmid, pWBG731, present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749 family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium, and penicillin resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS 257 , IS 257 -dependent miniature inverted-repeat transposable elements (MITEs), and the BinL resolution system of the β-lactamase transposon Tn 552 An evolutionarily intermediate ∼42-kb nonconjugative plasmid, pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline resistance plasmid pT181. IS 257 likely facilitated the replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized nonconjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous community-associated methicillin-sensitive S. aureus (CA-MSSA) isolates. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA., (Copyright © 2019 American Society for Microbiology.)
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- 2019
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43. Genomic, Antimicrobial Resistance, and Public Health Insights into Enterococcus spp. from Australian Chickens.
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O'Dea M, Sahibzada S, Jordan D, Laird T, Lee T, Hewson K, Pang S, Abraham R, Coombs GW, Harris T, Pavic A, and Abraham S
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- Animals, Australia epidemiology, Cecum microbiology, Enterococcus drug effects, Enterococcus faecalis drug effects, Enterococcus faecalis genetics, Enterococcus faecium drug effects, Enterococcus faecium genetics, Genome, Bacterial, Genomics, Gram-Positive Bacterial Infections microbiology, Humans, Microbial Sensitivity Tests, Phylogeny, Poultry Diseases epidemiology, Poultry Diseases microbiology, Sepsis microbiology, Whole Genome Sequencing, Anti-Bacterial Agents pharmacology, Chickens microbiology, Drug Resistance, Multiple, Bacterial, Enterococcus genetics, Gram-Positive Bacterial Infections veterinary, Public Health
- Abstract
Due to Australia's management of antimicrobial use in poultry, particularly the discontinued use of avoparcin for nearly 20 years, it is hypothesized that vancomycin-resistant enterococci associated with human disease are not derived from poultry isolates. This study evaluated antimicrobial resistance (AMR) of five enterococcal species isolated from Australian meat chickens, genomic features of Enterococcus faecium and Enterococcus faecalis , and the phylogenetic relationship of the poultry-derived E. faecium with isolates from human sepsis cases. All enterococcal isolates from chicken ceca were subjected to antimicrobial susceptibility testing. E. faecium and E. faecalis underwent whole-genome sequencing. E. faecium was compared at the core genome level to a collection of human isolates ( n = 677) obtained from cases of sepsis over a 2-year period spanning 2015 to 2016. Overall, 205 enterococci were isolated consisting of five different species. E. faecium was the most frequently isolated species (37.6%), followed by E. durans (29.7%), E. faecalis (20%), E. hirae (12.2%), and E. gallinarum (0.5%). All isolates were susceptible to vancomycin and gentamicin, while one isolate was linezolid resistant (MIC 16 mg/liter). Core genome analysis of the E. faecium demonstrated two clades consisting predominantly of human or chicken isolates in each clade, with minimal overlap. Principal component analysis for total gene content revealed three clusters comprised of vanA -positive, vanB -positive, and both vanA - and vanB -negative E. faecium populations. The results of this study provide strong evidence that Australian chicken E. faecium isolates are unlikely to be precursor strains to the currently circulating vancomycin-resistant strains being isolated in Australian hospitals., (Copyright © 2019 O’Dea et al.)
- Published
- 2019
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44. Genomic and Epidemiological Evidence of a Dominant Panton-Valentine Leucocidin-Positive Methicillin Resistant Staphylococcus aureus Lineage in Sri Lanka and Presence Among Isolates From the United Kingdom and Australia.
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McTavish SM, Snow SJ, Cook EC, Pichon B, Coleman S, Coombs GW, Pang S, Arias CA, Díaz L, Boldock E, Davies S, Udukala M, Kearns AM, Siribaddana S, and de Silva TI
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Australia epidemiology, Child, Child, Preschool, Female, Hospitals, Teaching, Humans, Infant, Male, Methicillin-Resistant Staphylococcus aureus genetics, Middle Aged, Molecular Epidemiology, Molecular Typing, Phylogeny, Prospective Studies, Sri Lanka epidemiology, United Kingdom epidemiology, Virulence Factors genetics, Whole Genome Sequencing, Young Adult, Bacterial Toxins genetics, Exotoxins genetics, Leukocidins genetics, Methicillin-Resistant Staphylococcus aureus classification, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
- Abstract
Objective: To undertake the first detailed genomic analysis of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Sri Lanka. Methods: A prospective observational study was performed on 94 MRSA isolates collected over a 4 months period from the Anuradhapura Teaching Hospital, Sri Lanka. Screening for mec A, mec C, and the Panton-Valentine leucocidin (PVL)-associated lukS-PV/lukF-PV genes and molecular characterization by spa typing was undertaken. Whole genome sequencing (WGS) and phylogenetic analysis was performed on selected multilocus sequence type (MLST) clonal complex 5 (CC5) isolates from Sri Lanka, England, Australia, and Argentina. Results: All 94 MRSA harbored the mecA gene. Nineteen spa types belonging to nine MLST clonal complexes were identified. Where origin of the sample was recorded, most isolates were from skin and soft tissue infections (70/91; 76.9%), with fewer causing bacteremia (16/91; 17.6%), empyema (3/91; 3.3%) and osteomyelitis (2/91; 2.2%). Sixty two (65.9%) isolates were PVL positive with the majority (56 isolates; 90.3%) belonging to a dominant CC5 lineage. This lineage, PVL-positive ST5-MRSA-IVc, was associated with both community and hospital-onset infections. Based on WGS, representative PVL-positive ST5-MRSA-IVc isolates from Sri Lanka, England and Australia formed a single phylogenetic clade, suggesting wide geographical circulation. Conclusions: We present the most detailed genomic analysis of MRSA isolated in Sri Lanka to date. The analysis identified a PVL-positive ST5-MRSA-IVc that is prevalent among MRSA causing clinical infections in Sri Lanka. Furthermore, this clone was also found among isolates from the United Kingdom and Australia.
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- 2019
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45. Candida auris Sternal Osteomyelitis in a Man from Kenya Visiting Australia, 2015.
- Author
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Heath CH, Dyer JR, Pang S, Coombs GW, and Gardam DJ
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- Aged, Australia, Bone and Bones diagnostic imaging, Bone and Bones microbiology, Candidiasis drug therapy, Candidiasis microbiology, Chronic Disease, Fatal Outcome, Humans, Kenya, Male, Osteomyelitis drug therapy, Osteomyelitis microbiology, Tomography, X-Ray Computed, Travel, Whole Genome Sequencing, Antifungal Agents administration & dosage, Candida isolation & purification, Candidiasis diagnostic imaging, Osteomyelitis diagnostic imaging, Triazoles administration & dosage
- Abstract
In Australia in 2015, Candida auris sternal osteomyelitis was diagnosed in a 65-year-old man with a history of intensive care treatment in Kenya in 2012 and without a history of cardiac surgery. The isolate was South Africa clade III. Clinicians should note that C. auris can cause low-grade disease years after colonization.
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- 2019
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46. Severe Disease Caused by Community-Associated MRSA ST398 Type V, Australia, 2017.
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Coombs GW, Pang S, Daley DA, Lee YT, Abraham S, and Leroi M
- Subjects
- Australia, Humans, Male, Methicillin-Resistant Staphylococcus aureus isolation & purification, Methicillin-Resistant Staphylococcus aureus pathogenicity, Middle Aged, Phylogeny, Singapore ethnology, Virulence, Whole Genome Sequencing, Community-Acquired Infections microbiology, Endocarditis microbiology, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections microbiology
- Abstract
Using whole-genome sequencing, we identified a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type (ST) 398 type V (5C2&5) isolate (typically found in China) in Australia in 2017. This CA-MRSA ST398 variant was highly virulent, similar to other related CA-MRSAs of ST398. This strain should be monitored to prevent more widespread dissemination.
- Published
- 2019
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47. Characterization of Staphylococcal Cassette Chromosome mec Elements from Methicillin-Resistant Staphylococcus pseudintermedius Infections in Australian Animals.
- Author
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Worthing KA, Schwendener S, Perreten V, Saputra S, Coombs GW, Pang S, Davies MR, Abraham S, Trott DJ, and Norris JM
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Australia, Computational Biology, Microbial Sensitivity Tests, Oxacillin pharmacology, Staphylococcal Infections microbiology, Staphylococcus drug effects, Staphylococcus isolation & purification, Whole Genome Sequencing, Animal Diseases microbiology, Chromosomes, Bacterial, Genomic Islands, Methicillin Resistance, Staphylococcal Infections veterinary, Staphylococcus genetics
- Abstract
We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome mec (SCC mec ) elements from 77 veterinary methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates. Isolates were characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCC mec elements, and a sixth novel element, were identified: SCC mec III (also known as II-III), ΨSCC mec
57395 , and SCC mecNA45 (a SCC mec VII variant), all previously described in MRSP, and SCC mec IVg and SCC mec VT , previously described in both methicillin-resistant Staphylococcus aureus (MRSA) and MRSP. The sixth element was novel and found among nine geographically clustered isolates. This novel pseudostaphylococcal cassette chromosome (ΨSCC mecKW21 ) contained a class A mec gene complex but lacked ccr genes. It also harbored heavy metal (cadmium) resistance determinants. The median oxacillin MIC values among ΨSCC mecKW21 , SCC mec III, and SCC mec VT isolates were significantly higher than those determined for the SCC mecNA45 VII variant isolates and ΨSCC mec57395 and SCC mec IVg isolates. ΨSCC mecKW21 was found exclusively in sequence type 497 (ST497), an MRSP clone that is locally successful in Victoria, Australia. Future studies are necessary to determine if this clone has disseminated further afield and if ΨSCC mecKW21 has moved into other MRSP lineages or staphylococcal species. IMPORTANCE Staphylococcus pseudintermedius is a significant veterinary pathogen and occasional cause of infections in humans. β-Lactams are an important group of antimicrobials used to treat staphylococcal infections in humans and animals. However, when staphylococci become methicillin resistant via the acquisition of a mobile genetic element called staphylococcal cassette chromosome mec (SCC mec ), they become resistant to all β-lactams. This study detected a novel SCC mec element among a cluster of methicillin-resistant S. pseudintermedius isolates from animals in Australia. It also detected SCC mec elements in S. pseudintermedius that had high similarity to those identified in methicillin-resistant Staphylococcus aureus , demonstrating how human and animal pathogens can share the same resistance determinants., (Copyright © 2018 Worthing et al.)- Published
- 2018
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48. Complete Genome Sequence of a Staphylococcus aureus Sequence Type 612 Isolate from an Australian Horse.
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Murphy RJT, Lee YT, Pang S, Bastholm TR, Crow JE, Davis AM, Coombs GW, O'Dea MA, Abraham S, and Ramsay JP
- Abstract
Staphylococcus aureus is a serious pathogen of humans and animals. Multilocus sequence type 612 is dominant and highly virulent in South African hospitals but relatively uncommon elsewhere. We present the complete genome sequence of methicillin-resistant Staphylococcus aureus strain SVH7513, isolated from a horse at a veterinary clinic in New South Wales, Australia.
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- 2018
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49. Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.
- Author
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van Hal SJ, Steinig EJ, Andersson P, Holden MTG, Harris SR, Nimmo GR, Williamson DA, Heffernan H, Ritchie SR, Kearns AM, Ellington MJ, Dickson E, de Lencastre H, Coombs GW, Bentley SD, Parkhill J, Holt DC, Giffard PM, and Tong SYC
- Abstract
Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCC mec ) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens.
- Published
- 2018
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50. Molecular Typing of ST239-MRSA-III From Diverse Geographic Locations and the Evolution of the SCC mec III Element During Its Intercontinental Spread.
- Author
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Monecke S, Slickers P, Gawlik D, Müller E, Reissig A, Ruppelt-Lorz A, Akpaka PE, Bandt D, Bes M, Boswihi SS, Coleman DC, Coombs GW, Dorneanu OS, Gostev VV, Ip M, Jamil B, Jatzwauk L, Narvaez M, Roberts R, Senok A, Shore AC, Sidorenko SV, Skakni L, Somily AM, Syed MA, Thürmer A, Udo EE, Vremerǎ T, Zurita J, and Ehricht R
- Abstract
ST239-MRSA-III is probably the oldest truly pandemic MRSA strain, circulating in many countries since the 1970s. It is still frequently isolated in some parts of the world although it has been replaced by other MRSA strains in, e.g., most of Europe. Previous genotyping work (Harris et al., 2010; Castillo-Ramírez et al., 2012) suggested a split in geographically defined clades. In the present study, a collection of 184 ST239-MRSA-III isolates, mainly from countries not covered by the previous studies were characterized using two DNA microarrays (i) targeting an extensive range of typing markers, virulence and resistance genes and (ii) a SCC mec subtyping array. Thirty additional isolates underwent whole-genome sequencing (WGS) and, together with published WGS data for 215 ST239-MRSA-III isolates, were analyzed using in-silico analysis for comparison with the microarray data and with special regard to variation within SCC mec elements. This permitted the assignment of isolates and sequences to 39 different SCC mec III subtypes, and to three major and several minor clades. One clade, characterized by the integration of a transposon into nsaB and by the loss of fnbB and splE was detected among isolates from Turkey, Romania and other Eastern European countries, Russia, Pakistan, and (mainly Northern) China. Another clade, harboring sasX/sesI is widespread in South-East Asia including China/Hong Kong, and surprisingly also in Trinidad & Tobago. A third, related, but sasX/sesI -negative clade occurs not only in Latin America but also in Russia and in the Middle East from where it apparently originated and from where it also was transferred to Ireland. Minor clades exist or existed in Western Europe and Greece, in Portugal, in Australia and New Zealand as well as in the Middle East. Isolates from countries where this strain is not epidemic (such as Germany) frequently are associated with foreign travel and/or hospitalization abroad. The wide dissemination of this strain and the fact that it was able to cause a hospital-borne pandemic that lasted nearly 50 years emphasizes the need for stringent infection prevention and control and admission screening.
- Published
- 2018
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