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2. Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Author

Xie, Ouli, Morris, Jacqueline M., Hayes, Andrew J., Towers, Rebecca J., Jespersen, Magnus G., Lees, John A., Ben Zakour, Nouri L., Berking, Olga, Baines, Sarah L., Carter, Glen P., Tonkin-Hill, Gerry, Schrieber, Layla, McIntyre, Liam, Lacey, Jake A., James, Taylah B., Sriprakash, Kadaba S., Beatson, Scott A., Hasegawa, Tadao, Giffard, Phil, Steer, Andrew C., Batzloff, Michael R., Beall, Bernard W., Pinho, Marcos D., Ramirez, Mario, Bessen, Debra E., Dougan, Gordon, Bentley, Stephen D., Walker, Mark J., Currie, Bart J., Tong, Steven Y. C., McMillan, David J., and Davies, Mark R.

Published
2024
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3. Global and local epidemiology of Group A Streptococcus indicates that naturally-acquired immunity is enduring and strain-specific

Author

Chisholm, Rebecca H., Lacey, Jake A., Kokko, Jan, Campbell, Patricia T., McDonald, Malcolm I., Corander, Jukka, Davies, Mark R., Tong, Steven Y. C., McVernon, Jodie, and Geard, Nicholas

Subjects
Quantitative Biology - Populations and Evolution
Abstract

The bacterium Group A Streptococcus (Streptococcus pyogenes, GAS) is a human-specific pathogen and a major cause of global morbidity and mortality. Despite decades of research our knowledge of GAS infection and immunity is incomplete, hampering vaccine design and other efforts to reduce disease prevalence. Epidemiological studies indicate positive associations between the prevalence of GAS-related disease, the diversity of circulating strains and the degree of poverty in host populations. However, the infection and immune mechanisms underlying these associations are not clear. In this work, we use an agent-based model to demonstrate that observed diversity and prevalence are best accounted for by the hypothesis that GAS infection confers enduring strain-specific immunity, with reduced or absent cross-protection against infection by other strains. Our results suggest that the success of GAS vaccines will depend on their ability to elicit long-lasting cross-protective immunity over multiple strain types.

Published
2021

6. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Author

Mu, Andre, Klare, William P., Baines, Sarah L., Ignatius Pang, C. N., Guérillot, Romain, Harbison-Price, Nichaela, Keller, Nadia, Wilksch, Jonathan, Nhu, Nguyen Thi Khanh, Phan, Minh-Duy, Keller, Bernhard, Nijagal, Brunda, Tull, Dedreia, Dayalan, Saravanan, Chua, Hwa Huat Charlie, Skoneczny, Dominik, Koval, Jason, Hachani, Abderrahman, Shah, Anup D., Neha, Nitika, Jadhav, Snehal, Partridge, Sally R., Cork, Amanda J., Peters, Kate, Bertolla, Olivia, Brouwer, Stephan, Hancock, Steven J., Álvarez-Fraga, Laura, De Oliveira, David M. P., Forde, Brian, Dale, Ashleigh, Mujchariyakul, Warasinee, Walsh, Calum J., Monk, Ian, Fitzgerald, Anna, Lum, Mabel, Correa-Ospina, Carolina, Roy Chowdhury, Piklu, Parton, Robert G., De Voss, James, Beckett, James, Monty, Francois, McKinnon, Jessica, Song, Xiaomin, Stephen, John R., Everest, Marie, Bellgard, Matt I., Tinning, Matthew, Leeming, Michael, Hocking, Dianna, Jebeli, Leila, Wang, Nancy, Ben Zakour, Nouri, Yasar, Serhat A., Vecchiarelli, Stefano, Russell, Tonia, Zaw, Thiri, Chen, Tyrone, Teng, Don, Kassir, Zena, Lithgow, Trevor, Jenney, Adam, Cole, Jason N., Nizet, Victor, Sorrell, Tania C., Peleg, Anton Y., Paterson, David L., Beatson, Scott A., Wu, Jemma, Molloy, Mark P., Syme, Anna E., Goode, Robert J. A., Hunter, Adam A., Bowland, Grahame, West, Nicholas P., Wilkins, Marc R., Djordjevic, Steven P., Davies, Mark R., Seemann, Torsten, Howden, Benjamin P., Pascovici, Dana, Tyagi, Sonika, Schittenhelm, Ralf B., De Souza, David P., McConville, Malcolm J., Iredell, Jonathan R., Cordwell, Stuart J., Strugnell, Richard A., Stinear, Timothy P., Schembri, Mark A., and Walker, Mark J.

Published
2023
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7. Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

Author

Davies, Mark R., Keller, Nadia, Brouwer, Stephan, Jespersen, Magnus G., Cork, Amanda J., Hayes, Andrew J., Pitt, Miranda E., De Oliveira, David M. P., Harbison-Price, Nichaela, Bertolla, Olivia M., Mediati, Daniel G., Curren, Bodie F., Taiaroa, George, Lacey, Jake A., Smith, Helen V., Fang, Ning-Xia, Coin, Lachlan J. M., Stevens, Kerrie, Tong, Steven Y. C., Sanderson-Smith, Martina, Tree, Jai J., Irwin, Adam D., Grimwood, Keith, Howden, Benjamin P., Jennison, Amy V., and Walker, Mark J.

Published
2023
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8. Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analysis

Author

Lacey, Jake A, Marcato, Adrian J, Chisholm, Rebecca H, Campbell, Patricia T, Zachreson, Cameron, Price, David J, James, Taylah B, Morris, Jacqueline M, Gorrie, Claire L, McDonald, Malcolm I, Bowen, Asha C, Giffard, Philip M, Holt, Deborah C, Currie, Bart J, Carapetis, Jonathan R, Andrews, Ross M, Davies, Mark R, Geard, Nicholas, McVernon, Jodie, and Tong, Steven Y C

Published
2023
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9. Genomic epidemiology of Salmonella Typhi in Central Division, Fiji, 2012 to 2016

Author

Davies, Mark R., Duchene, Sebastian, Valcanis, Mary, Jenkins, Aaron P., Jenney, Adam, Rosa, Varanisese, Hayes, Andrew J., Strobel, Aneley Getahun, McIntyre, Liam, Lacey, Jake A., Klemm, Elizabeth J., Wong, Vanessa K., Sahukhan, Aalisha, Thomson, Helen, Page, Andrew, Hocking, Dianna, Wang, Nancy, Tudravu, Litia, Rafai, Eric, Dougan, Gordon, Howden, Benjamin P., Crump, John A., Mulholland, Kim, and Strugnell, Richard A.

Published
2022
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12. Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence.

Author

Deneubourg, Geoffrey, Schiavolin, Lionel, Lakhloufi, Dalila, Botquin, Gwenaelle, Delforge, Valérie, Davies, Mark R., Smeesters, Pierre R., and Botteaux, Anne

Subjects
NECROTIZING fasciitis, STREPTOCOCCUS pyogenes, PHENOTYPES, PHAGOCYTOSIS, GENOMES, TRANSPOSONS
Abstract

Streptococcus pyogenes, or Group A Streptococcus (GAS), is responsible for over 500,000 deaths per year. Approximately 15% of these deaths are caused by necrotizing soft-tissue infections. In 2008, we isolated an M5 GAS, named the LO1 strain, responsible for the nosocomial transmission of necrotizing fasciitis between a baby and a nurse in Belgium. To understand this unusual transmission route, the LO1 strain was sequenced. A comparison of the LO1 genome and transcriptome with the reference M5 Manfredo strain was conducted. We found that the major differences were the presence of an additional DNase and a Tn916-like transposon in the LO1 and other invasive M5 genomes. RNA-seq analysis showed that genes present on the transposon were barely expressed. In contrast, the DNases presented different expression profiles depending on the tested conditions. We generated knock-out mutants in the LO1 background and characterized their virulence phenotype. We also determined their nuclease activity on different substrates. We found that DNases are dispensable for biofilm formation and adhesion to both keratinocytes and pharyngeal cells. Three of these were found to be essential for blood survival; Spd4 and Sdn are implicated in phagocytosis resistance, and Spd1 is responsible for neutrophil extracellular trap (NET) degradation. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Clinical Snapshot of Group A Streptococcal Isolates from an Australian Tertiary Hospital.

Author

Shaw, Phoebe K., Hayes, Andrew J., Langton, Maree, Berkhout, Angela, Grimwood, Keith, Davies, Mark R., Walker, Mark J., and Brouwer, Stephan

Subjects
SCARLATINA, TOXIC shock syndrome, COVID-19 pandemic, NECROTIZING fasciitis, WHOLE genome sequencing
Abstract

Streptococcus pyogenes (Group A Streptococcus, GAS) is a human-restricted pathogen that causes a wide range of diseases from pharyngitis and scarlet fever to more severe, invasive infections such as necrotising fasciitis and streptococcal toxic shock syndrome. There has been a global increase in both scarlet fever and invasive infections during the COVID-19 post-pandemic period. The aim of this study was the molecular characterisation of 17 invasive and non-invasive clinical non-emm1 GAS isolates from an Australian tertiary hospital collected between 2021 and 2022. Whole genome sequencing revealed a total of nine different GAS emm types with the most prevalent being emm22, emm12 and emm3 (each 3/17, 18%). Most isolates (14/17, 82%) carried at least one superantigen gene associated with contemporary scarlet fever outbreaks, and the carriage of these toxin genes was non-emm type specific. Several mutations within key regulatory genes were identified across the different GAS isolates, which may be linked to an increased expression of several virulence factors. This study from a single Australian centre provides a snapshot of non-emm1 GAS clinical isolates that are multiclonal and linked with distinct epidemiological markers commonly observed in high-income settings. These findings highlight the need for continual surveillance to monitor genetic markers that may drive future outbreaks. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A Streptococcus

Author

Henningham, Anna, Davies, Mark R, Uchiyama, Satoshi, van Sorge, Nina M, Lund, Sean, Chen, Kelsey T, Walker, Mark J, Cole, Jason N, and Nizet, Victor

Subjects
Biodefense, Clinical Research, Prevention, Emerging Infectious Diseases, Vaccine Related, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Acetylglucosamine, Animals, Antigens, Bacterial, Blood Bactericidal Activity, Cell Wall, Disease Models, Animal, Gene Deletion, Humans, Mice, Polysaccharides, Bacterial, Streptococcal Infections, Streptococcus pyogenes, Survival Analysis, Virulence, Virulence Factors, group A carbohydrate, group A Streptococcus, Lancefield antigen, virulence factor, innate immunity, Microbiology
Abstract

Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. We previously identified the 12-gene GAC biosynthesis gene cluster and determined that the glycosyltransferase GacI was required for addition of the GlcNAc side chain to the polyrhamnose core. Loss of the GAC GlcNAc epitope in serotype M1 GAS resulted in attenuated virulence in two animal infection models and increased GAS sensitivity to killing by whole human blood, serum, neutrophils, and antimicrobial peptides. Here, we report that the GAC biosynthesis gene cluster is ubiquitous among 520 GAS isolates from global sources, representing 105 GAS emm serotypes. Isogenic ΔgacI mutants were constructed in M2, M3, M4, M28, and M89 backgrounds and displayed an array of phenotypes in susceptibility to killing by whole human blood, baby rabbit serum, human platelet releasate, human neutrophils, and antimicrobial peptide LL-37. The contribution of the GlcNAc side chain to GAS survival in vivo also varied by strain, demonstrating that it is not a prerequisite for virulence in the murine infection model. Thus, the relative contribution of GAC to virulence in non-M1 serotypes appears to depend on the quorum of other virulence factors that each strain possesses.IMPORTANCE The Lancefield group A carbohydrate (GAC) is the species-defining antigen for group A Streptococcus (GAS), comprising ~50% of the cell wall of this major human pathogen. We previously showed that the GlcNAc side chain of GAC contributes to the innate immune resistance and animal virulence phenotypes of the globally disseminated strain of serotype M1 GAS. Here, we use isogenic mutagenesis to examine the role of GAC GlcNAc in five additional medically relevant GAS serotypes. Overall, the GlcNAc side chain of GAC contributes to the innate immune resistance of GAS, but the relative contribution varies among individual strains. Moreover, the GAC GlcNAc side chain is not a universal prerequisite for GAS virulence in the animal model.

Published
2018

16. Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter

Author

Rodrigo, M. Kalindu D., Saiganesh, Aarti, Hayes, Andrew J., Wilson, Alisha M., Anstey, Jack, Pickering, Janessa L., Iwasaki, Jua, Hillas, Jessica, Winslow, Scott, Woodman, Tabitha, Nitschke, Philipp, Lacey, Jake A., Breese, Karen J., van der Linden, Mark P. G., Giffard, Philip M., Tong, Steven Y. C., Gray, Nicola, Stubbs, Keith A., Carapetis, Jonathan R., Bowen, Asha C., Davies, Mark R., and Barnett, Timothy C.

Published
2022
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23. Biphasic Outbreak of Invasive Group A Streptococcus Disease in Eldercare Facility, New Zealand

Author

Worthing, Kate A., Werno, Anja, Pink, Ramon, McIntyre, Liam, Carter, Glen P., Williamson, Deborah A., and Davies, Mark R.

Subjects
Oxacillin -- Analysis -- Health aspects, Microbial drug resistance -- Analysis -- Health aspects, Genomes -- Analysis -- Health aspects, Epidemiology -- Analysis -- Health aspects, Genomics -- Health aspects -- Analysis, Methicillin -- Health aspects -- Analysis, Genetic research, DNA sequencing, Computational biology, Diseases, Health
Abstract

Streptococcus pyogenes, or group A Streptococcus (GAS), is a gram-positive, human-adapted opportunistic bacterial pathogen. GAS causes a wide variety of clinical manifestations, from relatively benign self-limiting infections of the nasopharynx [...]

Published
2020
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26. The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Author

van Sorge, Nina M, Cole, Jason N, Kuipers, Kirsten, Henningham, Anna, Aziz, Ramy K, Kasirer-Friede, Ana, Lin, Leo, Berends, Evelien TM, Davies, Mark R, Dougan, Gordon, Zhang, Fan, Dahesh, Samira, Shaw, Laura, Gin, Jennifer, Cunningham, Madeleine, Merriman, Joseph A, Hütter, Julia, Lepenies, Bernd, Rooijakkers, Suzan HM, Malley, Richard, Walker, Mark J, Shattil, Sanford J, Schlievert, Patrick M, Choudhury, Biswa, and Nizet, Victor

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Research, Emerging Infectious Diseases, Vaccine Related, Infectious Diseases, Immunization, Prevention, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Acetylglucosamine, Animals, Antibodies, Bacterial, Antigens, Bacterial, Antimicrobial Cationic Peptides, Bacterial Proteins, Carbohydrates, Cathelicidins, Epitopes, Female, Glycosyltransferases, Host-Pathogen Interactions, Humans, Immunity, Innate, Male, Mice, Inbred Strains, Mutagenesis, Neutrophils, Rabbits, Streptococcal Infections, Streptococcal Vaccines, Streptococcus pyogenes, Virulence Factors, Microbiology, Immunology, Biochemistry and cell biology, Medical microbiology
Abstract

Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes, gacA through gacL. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAc side-chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum, and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis, and a deeper understanding of this unique polysaccharide has implications for vaccine development.

Published
2014

27. Genetic heterogeneity in theSalmonellaTyphi Vi capsule locus: A population genomic study from Fiji

Author

Getahun Strobel, Aneley, primary, Hayes, Andrew J., additional, Wirth, Wytamma, additional, Mua, Mikaele, additional, Saumalua, Tiko, additional, Cabenatabua, Orisi, additional, Soqo, Vika, additional, Rosa, Varanisese, additional, Wang, Nancy, additional, Lacey, Jake A., additional, Hocking, Dianna, additional, Valcanis, Mary, additional, Jenney, Adam, additional, Howden, Benjamin P., additional, Duchene, Sebastian, additional, Mulholland, Kim, additional, Strugnell, Richard A., additional, and Davies, Mark R., additional

Published
2023
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31. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

Author

Davies, Mark R., McIntyre, Liam, Mutreja, Ankur, Lacey, Jake A., Lees, John A., Towers, Rebecca J., Duchêne, Sebastián, Smeesters, Pierre R., Frost, Hannah R., Price, David J., Holden, Matthew T. G., David, Sophia, Giffard, Philip M., Worthing, Kate A., Seale, Anna C., Berkley, James A., Harris, Simon R., Rivera-Hernandez, Tania, Berking, Olga, Cork, Amanda J., Torres, Rosângela S. L. A., Lithgow, Trevor, Strugnell, Richard A., Bergmann, Rene, Nitsche-Schmitz, Patric, Chhatwal, Gusharan S., Bentley, Stephen D., Fraser, John D., Moreland, Nicole J., Carapetis, Jonathan R., Steer, Andrew C., Parkhill, Julian, Saul, Allan, Williamson, Deborah A., Currie, Bart J., Tong, Steven Y. C., Dougan, Gordon, and Walker, Mark J.

Published
2019
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33. Overlapping transmission of group A and C/G Streptococcus facilitates inter-species mobile genetic element exchange

Author

Xie, Ouli, primary, Zachreson, Cameron, additional, Tonkin-Hill, Gerry, additional, Price, David J, additional, Lacey, Jake A, additional, Morris, Jacqueline M, additional, McDonald, Malcolm I, additional, Bowen, Asha C, additional, Giffard, Philip M, additional, Currie, Bart J, additional, Carapetis, Jonathan R, additional, Holt, Deborah C, additional, Bentley, Stephen D, additional, Davies, Mark R, additional, and Tong, Steven YC, additional

Published
2023
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34. Inter-species gene flow drives ongoing evolution ofStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis

Author

Xie, Ouli, primary, Morris, Jacqueline M., additional, Hayes, Andrew J., additional, Towers, Rebecca J., additional, Jespersen, Magnus G., additional, Lees, John A., additional, Ben Zakour, Nouri L., additional, Berking, Olga, additional, Baines, Sarah L., additional, Carter, Glen P., additional, Tonkin-Hill, Gerry, additional, Schrieber, Layla, additional, McIntyre, Liam, additional, Lacey, Jake A., additional, James, Taylah B., additional, Sriprakash, Kadaba S., additional, Beatson, Scott A., additional, Hasegawa, Tadao, additional, Giffard, Phil, additional, Steer, Andrew C., additional, Batzloff, Michael R., additional, Beall, Bernie W., additional, Pinho, Marcos D., additional, Ramirez, Mario, additional, Bessen, Debra E., additional, Dougan, Gordon, additional, Bentley, Stephen D., additional, Walker, Mark J., additional, Currie, Bart J., additional, Tong, Steven Y. C., additional, McMillan, David J., additional, and Davies, Mark R., additional

Published
2023
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35. Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

Author

Brouwer, Stephan, Barnett, Timothy C., Ly, Diane, Kasper, Katherine J., De Oliveira, David M. P., Rivera-Hernandez, Tania, Cork, Amanda J., McIntyre, Liam, Jespersen, Magnus G., Richter, Johanna, Schulz, Benjamin L., Dougan, Gordon, Nizet, Victor, Yuen, Kwok-Yung, You, Yuanhai, McCormick, John K., Sanderson-Smith, Martina L., Davies, Mark R., and Walker, Mark J.

Published
2020
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36. The Clinical Significance of Anterior Horn Meniscal Tears Diagnosed on Magnetic Resonance Images*

Author

Shepard, Michael F, Hunter, David M, Davies, Mark R, Shapiro, Matthew S, and Seeger, Leanne L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Evaluation of treatments and therapeutic interventions, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 6.4 Surgery, Adolescent, Adult, Aged, Aged, 80 and over, Arthroscopy, Humans, Knee Injuries, Magnetic Resonance Imaging, Menisci, Tibial, Middle Aged, Retrospective Studies, Rupture, Tibial Meniscus Injuries, Biomedical Engineering, Mechanical Engineering, Human Movement and Sports Sciences, Orthopedics, Clinical sciences, Allied health and rehabilitation science, Sports science and exercise
Abstract

We assessed the accuracy of magnetic resonance imaging in detecting clinically significant lesions of the anterior horn of the meniscus by reviewing 947 consecutive knee magnetic resonance imaging reports. Of these, 76 (8%) indicated a tear of the anterior horn of the medial or lateral meniscus. Thirty-one of these 76 patients underwent a subsequent arthroscopic examination, and their operative reports were reviewed. The 45 patients who were not examined arthroscopically were contacted and interviewed for clinical follow-up. Among the 31 patients who underwent arthroscopic examination, 8 anterior horn tears were noted in the predicted area (26% true-positive results), 23 patients had intact anterior horns (74% false-positive results), and 18 had normal intact menisci in all zones. Of the 45 patients who did not undergo arthroscopic surgery, 6 had isolated anterior horn tears reported on magnetic resonance imaging, and 5 of the 6 were asymptomatic at follow-up. The other 39 patients had multiple pathologic conditions noted on the magnetic resonance imaging report and continued to report knee pain at the follow-up interview. Increased signal intensity at the anterior horn of the meniscus seen on magnetic resonance imaging commonly does not represent a clinically significant lesion. We recommend correlation with the physical examination when interpreting this "positive" finding on knee magnetic resonance imaging examinations.

Published
2002

37. Promiscuous evolution of Group A Streptococcal M and M-like proteins.

Author

Frost, Hannah, Guglielmini, Julien, Duchêne, Sebastian, Lacey, Jake A., Sanderson-Smith, Martina L, Steer, Andrew C, Walker, Mark J, Botteaux, Anne, Davies, Mark R, Smeesters, Pierre, Frost, Hannah, Guglielmini, Julien, Duchêne, Sebastian, Lacey, Jake A., Sanderson-Smith, Martina L, Steer, Andrew C, Walker, Mark J, Botteaux, Anne, Davies, Mark R, and Smeesters, Pierre

Abstract

Group A Streptococcus (GAS) M and M-like proteins are essential virulence factors and represent the primary epidemiological marker of this pathogen. Protein sequences encoding 1054 M, Mrp and Enn proteins, from 1668 GAS genomes, were analysed by SplitsTree4, partitioning around medoids and co-occurrence. The splits network and groups-based analysis of all M and M-like proteins revealed four large protein groupings, with multiple evolutionary histories as represented by multiple edges for most splits, leading to 'M-family-groups' (FG) of protein sequences: FG I, Mrp; FG II, M protein and Protein H; FG III, Enn; and FG IV, M protein. M and Enn proteins formed two groups with nine sub-groups and Mrp proteins formed four groups with ten sub-groups. Discrete co-occurrence of M and M-like proteins were identified suggesting that while dynamic, evolution may be constrained by a combination of functional and virulence attributes. At a granular level, four distinct family-groups of M, Enn and Mrp proteins are observable, with Mrp representing the most genetically distinct of the family-group of proteins. While M and Enn protein families generally group into three distinct family-groups, horizontal and vertical gene flow between distinct GAS strains is ongoing., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

39. Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models

Author

Langshaw, Emma L., primary, Reynolds, Simone, additional, Ozberk, Victoria, additional, Dooley, Jessica, additional, Calcutt, Ainslie, additional, Zaman, Mehfuz, additional, Walker, Mark J., additional, Batzloff, Michael R., additional, Davies, Mark R., additional, Good, Michael F., additional, and Pandey, Manisha, additional

Published
2023
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40. Promiscuous evolution of Group A Streptococcal M and M-like proteins

Author

Frost, Hannah R., primary, Guglielmini, Julien, additional, Duchêne, Sebastian, additional, Lacey, Jake A., additional, Sanderson-Smith, Martina, additional, Steer, Andrew C., additional, Walker, Mark J., additional, Botteaux, Anne, additional, Davies, Mark R., additional, and Smeesters, Pierre R., additional

Published
2023
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43. Invasive group A Streptococcus infection among children, rural Kenya

Author

Seale, Anna C., Davies, Mark R., Anampiu, Kirimi, Morpeth, Susan C., Nyongesa, Sammy, Mwarumba, Salim, Smeesters, Pierre R., Efstratiou, Androulla, Karugutu, Rosylene, Mturi, Neema, Williams, Thomas N., Scott, J. Anthony G., Kariuki, Samuel, Dougan, Gordon, and Berkley, James A.

Subjects
Bacterial pneumonia -- Analysis, Genomics -- Analysis, Pneumonia -- Analysis, Health
Abstract

Worldwide, childhood deaths have decreased, largely attributable to fewer deaths from pneumonia, measles, and diarrhea (1); some of these reductions have been achieved through vaccination against common bacterial pathogens such [...]

Published
2016
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44. Genomic epidemiology of Salmonella Typhi in Central Division, Fiji, 2012 to 2016

Author

Davies, Mark R, Duchene, Sebastian, Valcanis, Mary, Jenkins, Aaron P, Jenney, Adam, Rosa, Varanisese, Hayes, Andrew J, Strobel, Aneley Getahun, McIntyre, Liam, Lacey, Jake A, Klemm, Elizabeth J, Wong, Vanessa K, Sahukhan, Aalisha, Thomson, Helen, Page, Andrew, Hocking, Dianna, Wang, Nancy, Tudravu, Litia, Rafai, Eric, Dougan, Gordon, Howden, Benjamin P, Crump, John A, Mulholland, Kim, Strugnell, Richard A, Dougan, Gordon [0000-0003-0022-965X], and Apollo - University of Cambridge Repository

Subjects
Public health, Fiji, Outbreak, Population genomics, Bayesian, Phylodynamics, Salmonella Typhi, Phylogeny, Typhoid fever
Abstract

BACKGROUND: Typhoid fever is endemic in some Pacific Island Countries including Fiji and Samoa yet genomic surveillance is not routine in such settings. Previous studies suggested imports of the global H58 clade of Salmonella enterica var Typhi (Salmonella Typhi) contribute to disease in these countries which, given the MDR potential of H58, does not auger well for treatment. The objective of the study was to define the genomic epidemiology of Salmonella Typhi in Fiji. METHODS: Genomic sequencing approaches were implemented to study the distribution of 255 Salmonella Typhi isolates from the Central Division of Fiji. We augmented epidemiological surveillance and Bayesian phylogenomic approaches with a multi-year typhoid case-control study to define geospatial patterns among typhoid cases. FINDINGS: Genomic analyses showed Salmonella Typhi from Fiji resolved into 2 non-H58 genotypes with isolates from the two dominant ethnic groups, the Indigenous (iTaukei) and non-iTaukei genetically indistinguishable. Low rates of international importation of clones was observed and overall, there were very low levels an antibiotic resistance within the endemic Fijian typhoid genotypes. Genomic epidemiological investigations were able to identify previously unlinked case clusters. Bayesian phylodynamic analyses suggested that genomic variation within the larger endemic Salmonella Typhi genotype expanded at discreet times, then contracted. INTERPRETATION: Cyclones and flooding drove 'waves' of typhoid outbreaks in Fiji which, through population aggregation, poor sanitation and water safety, and then mobility of the population, spread clones more widely. Minimal international importations of new typhoid clones suggest that targeted local intervention strategies may be useful in controlling endemic typhoid infection. These findings add to our understanding of typhoid transmission networks in an endemic island country with broad implications, particularly across Pacific Island Countries. FUNDING: This work was supported by the Coalition Against Typhoid through the Bill and Melinda Gates Foundation [grant number OPP1017518], the Victorian Government, the National Health and Medical Research Council Australia, the Australian Research Council, and the Fiji Ministry of Health and Medical Services.

Published
2022
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47. The Legal Implications of Student Use of Social Networking Sites in the UK and US: Current Concerns and Lessons for the Future

Author

Davies, Mark R. and Lee, Barbara A.

Abstract

This paper provides a comparative snapshot of the current state of the law in the US and UK with respect to potential liability of university and college students for use (and misuse) of social networking sites. It reviews the limited case law on this topic, highlights the differences in the two nations' laws of defamation and the various possible legal claims available to individuals allegedly harmed by postings on these social networking sites, and concludes that neither country currently offers a satisfactory legal or quasi-legal model for resolving these disputes. (Contains 137 notes.)

Published
2008
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48. Molecular Characterization of the 2011 Hong Kong Scarlet Fever Outbreak

Author

Tse, Herman, Bao, Jessie Y. J., Davies, Mark R., Maamary, Peter, Tsoi, Hoi-Wah, Tong, Amy H. Y., Ho, Tom C. C., Lin, Chi-Ho, Gillen, Christine M., Barnett, Timothy C., Chen, Jonathan H. K., Lee, Mianne, Yam, Wing-Cheong, Wong, Chi-Kin, Ong, Cheryl-Iynn Y., Chan, Yee-Wai, Wu, Cheng-Wei, Ng, Tony, Lim, Wilina W. L., Tsang, Thomas H. F., Tse, Cindy W. S., Dougan, Gordon, Walker, Mark J., Lok, Si, and Yuen, Kwok-Yung

Published
2012
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49. Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

Author

Davies, Mark R., McIntyre, Liam, Mutreja, Ankur, Lacey, Jake A., Lees, John A., Towers, Rebecca J., Duchêne, Sebastián, Smeesters, Pierre R., Frost, Hannah R., Price, David J., Holden, Matthew T. G., David, Sophia, Giffard, Philip M., Worthing, Kate A., Seale, Anna C., Berkley, James A., Harris, Simon R., Rivera-Hernandez, Tania, Berking, Olga, Cork, Amanda J., Torres, Rosângela S. L. A., Lithgow, Trevor, Strugnell, Richard A., Bergmann, Rene, Nitsche-Schmitz, Patric, Chhatwal, Gusharan S., Bentley, Stephen D., Fraser, John D., Moreland, Nicole J., Carapetis, Jonathan R., Steer, Andrew C., Parkhill, Julian, Saul, Allan, Williamson, Deborah A., Currie, Bart J., Tong, Steven Y. C., Dougan, Gordon, and Walker, Mark J.

Published
2019
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