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Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF., Competing Interests: The authors declare no conflict of interest.

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages-many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus , respectively.

Whereas the emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) in animal husbandry and its transmission to humans are well documented, less is known about factors driving the epidemic spread of this zoonotic lineage within the human population. One factor could be the bacteriophage phi3, which is rarely detected in S. aureus isolates from animals but commonly found among isolates from humans, including those of the human-adapted methicillin-susceptible S. aureus (MSSA) CC398 clade. The proportion of phi3-carrying MRSA spa -CC011 isolates, which constitute presumptively LA-MRSA within the multilocus sequence type (MLST) clonal complex 398, was systematically assessed for a period of 16 years to investigate the role of phi3 in the adaptation process of LA-MRSA to the human host. For this purpose, 632 MRSA spa -CC011 isolates from patients of a university hospital located in a pig farming-dense area in Germany were analyzed. Livestock-associated acquisition of MRSA spa -CC011 was previously reported as having increased from 1.8% in 2000 to 29.4% in 2014 in MRSA-positive patients admitted to this hospital. However, in this study, the proportion of phi3-carrying isolates rose only from 1.1% (2000 to 2006) to 3.9% (2007 to 2015). Characterization of the phi3 genomes revealed 12 different phage types ranging in size from 40,712 kb up to 44,003 kb, with four hitherto unknown integration sites (genes or intergenic regions) and several modified bacterial attachment ( attB ) sites. In contrast to the MSSA CC398 clade, phi3 acquisition seems to be no major driver for the readaptation of MRSA spa-CC011 to the human host., (Copyright © 2018 American Society for Microbiology.)

Problem Addressed: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), particularly of the clonal complex (CC) 398, emerged as zoonotic pathogens predominantly among humans with direct or indirect livestock contact, but also in healthcare settings. The factors contributing to the success of LA-MRSA are only poorly understood., Objective: During the past years, the use of heavy metal compounds as feed-supplements was found to influence the co-selection of LA-MRSA in pig herds. This study aimed to determine the prevalence of zinc resistance among MRSA CC398 isolated from patients of a German university hospital located in a pig farming-dense area., Methods and Approach: In comparison to concurrent healthcare-associated MRSA (HA-MRSA), LA-MRSA CC398 comprising isolates from their first appearance in 2000 to recent isolates from 2014 were included., Results: Among MRSA CC398, the overall resistance rate towards zinc chloride was 57% compared to only 3% among concurrently isolated HA-MRSA. Zinc resistance correlated with the presence of the czrC gene in 100% of the MRSA CC398 and in 67% of the HA-MRSA., Conclusions: The zinc resistance rate in MRSA CC398 significantly increased from 2009 to 2014 with a maximum in 2014. Alarmingly, zinc resistance has become a frequent phenotype of human LA-MRSA in Germany potentially facilitating co-selection of antibiotic resistance genes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

During cefoxitin-based nasal screening, phenotypically categorized methicillin-resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the presence of the mecA and mecC genes as well as for the SCCmec-orfX junction region. The isolate was found to carry a mecB gene previously described for Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked by β-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an 84.6-kb multidrug-resistance plasmid that harbors genes encoding additional resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides (ermB) and tetracyclines (tetS). This further plasmidborne β-lactam resistance mechanism harbors the putative risk of acceleration or reacceleration of MRSA spread, resulting in broad ineffectiveness of β-lactams as a main therapeutic application against staphylococcal infections.

The presence of methicillin-resistant Staphylococcus aureus (MRSA) CC398 in livestock and their transmission to humans followed by their introduction into hospitals led to a significant burden for the human healthcare system, especially in regions with a high density of livestock breeding. The CC398 lineage made two host changes in its evolutionary history: From humans to pigs and other livestock-associated animals and back to the human host. These adaptation processes are mirrored by changes of the equipment with virulence factors necessary for successful host change. Here, we consider these factors and their special role during human colonization and infection. Host adaptation of S. aureus CC398 is accompanied by genetic changes that are mainly driven by exchanges of mobile genetic elements. So far, it is not clear, which virulence or adhesion factors are important for S. aureus CC398 in host interaction. Among human and animal-derived MRSA CC398 virulence factors, e.g. (entero-) toxins, were rarely found. Overall, this review provides a comprehensive overview on the emerging S. aureus lineage CC398 by summarizing current knowledge from microbiological, molecular and cellular interaction studies in relation to clinical and epidemiological perspectives., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Colonization with livestock-associated Methicillin-resistant Staphylococcusaureus (LA-MRSA) among persons occupationally exposed to pigs, cattle or poultry is very frequent. In Europe, LA-MRSA mostly belong to the clonal lineage CC398. Since colonized persons have an increased risk of developing MRSA infections, defining the burden of work-related infection caused by LA-MRSA CC398 is of interest to exposed personnel, insurance companies and infection control staff. This review summarizes data on the types of occupation-related infections caused by LA-MRSA CC398, the incidence of such infections as well as potential preventive strategies. We identified twelve case reports on infections among livestock-exposed persons. Overall, there is a lack of data describing the incidence of occupation-related infections due to MRSA CC398. Currently, no specific guidance towards the prevention of LA-MRSA CC398 colonization of persons with routine exposure exists. In vitro, MRSA CC398 strains are susceptible (>95%) to mupirocin. Single reports have described effective decolonization of persons carrying LA-MRSA CC398, but long-term success rates are low in case of continuous livestock contact. Overall, the occupational health risk due to LA-MRSA CC398 is not well understood. Currently, prevention of human LA-MRSA CC398 infection is mostly based on the recommendation to perform screening and decolonization therapies prior to elective medical interventions in order to avoid nosocomial infections, but there is no conclusive evidence to perform specific measures aiming to forestall community-acquired infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

An advanced methicillin-resistant Staphylococcus aureus (MRSA) detection PCR approach targeting SCCmec-orfX along with mecA and mecC was evaluated for S. aureus and coagulase-negative staphylococci. The possession of mecA and/or mecC was correctly confirmed in all cases. All methicillin-susceptible S. aureus strains (n = 98; including staphylococcal cassette chromosome mec element [SCCmec] remnants) and 98.1% of the MRSA strains (n = 160, including 10 mecC-positive MRSA) were accurately categorized., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)