Abstract
BackgroundStaphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin–resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all β-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates.ResultsTo gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages ΦSa2usa and ΦSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone.ConclusionsWe observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1145) contains supplementary material, which is available to authorized users.
Highlights
Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections
Among sequenced S. aureus isolates, the arginine catabolic mobile element (ACME) is present in most USA300 strains circulating in the United States, but not USA400 isolates [22]
The completely sequenced USA300_FPR3757 strain was used as a reference for comparison to USA300 isolates, whereas USA400 strains were compared to S. aureus USA400 strain MW2
Summary
Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. The virulent nature of S. aureus is mediated by a wide array of cell surface proteins, secreted toxins and mobile genetic elements [15, 25,26,27,28,29,30,31] As such there are at least two possible explanations for the virulence of USA300. ACME encodes an arginine deiminase gene, called arcA that allows for enhanced survival in acidic environments [34] This process drives the synthesis of host polyamines that are toxic to S. aureus. It is likely not a coincidence that ACME encodes a spermine acetyl transferase, speG, which counteracts the toxic effects of polyamines In this regard, ACME appears to at least partially account for the observed pathogenesis of USA300 in skin infection [35,36]. ACME-deficient USA300 clinical isolates have been described supporting the data from animal models that ACME is not a necessary component of pathogencity or survival in humans
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
