Abstract
BackgroundSevere infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA.MethodsWe used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs.ResultsWe report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains.ConclusionsOur study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose.
Highlights
Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-Methicillin-resistant Staphylococcus aureus (MRSA)) are a global problem
Our findings emphasize the importance of the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process
Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose
Summary
We used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. All 185 S. aureus isolates obtained at Shanghai Children's Medical Center in 2012 were included. Bacterial strains of animal origin were collected from the Shanghai Animal Disease Prevention and Control Center, which is responsible for monitoring the epidemiology of animal infection in eastern China (see Additional file 1: Figure S1 for geographic matching of human and animal isolate sources). CA-S. aureus was defined as an isolate that was obtained either from an outpatient or from an inpatient (including those from general and urgent care and emergency rooms) ≤ 24 h after hospital admission and for which the patient lacked risk factors (contact with the hospital environment in the 6 months preceding the culture, S. aureus infection history or residence in a long-term care facility in the 12 months preceding the culture, presence of a central vascular catheter at the time of infection, and antibiotic use within at least 1 month preceding isolate collection, as determined by the review of medical records). One isolate could not be recovered for the in-depth analysis performed in our study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
