Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains

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.

Comparative RNA-seq-Based Transcriptome Analysis of the Virulence Characteristics of Methicillin-Resistant and -Susceptible Staphylococcus pseudintermedius Strains Isolated from Small Animals

“…One clue to this occurrence may be related to the upregulation of the entire arc operon in the MSSP isolate studied here. A similar operon has been found in other staphylococcal species, and in S. aureus, arcA (which belongs to the arc operon) encodes an arginine deaminase, which allows for enhanced survival in acidic environments (26). The upregulation of this operon may improve survival and promote biofilm formation of MSSP in acidic circumstances, such as in BHIB medium with glucose (which has a more acidic pH than BHIB medium alone or with NaCl).…”

“…The upregulation of this operon may improve survival and promote biofilm formation of MSSP in acidic circumstances, such as in BHIB medium with glucose (which has a more acidic pH than BHIB medium alone or with NaCl). During the early emergence of community-acquired MRSA, the USA300 (ST8) lineage disseminated rapidly and was considered hypervirulent, compared with lineages like MRSA USA400 (ST1) (26). However, USA300 does not contain many more virulence genes than USA400, but it does have an alteration in the expression of regulatory genes and increased expression of certain virulence genes (26).…”

“…During the early emergence of community-acquired MRSA, the USA300 (ST8) lineage disseminated rapidly and was considered hypervirulent, compared with lineages like MRSA USA400 (ST1) (26). However, USA300 does not contain many more virulence genes than USA400, but it does have an alteration in the expression of regulatory genes and increased expression of certain virulence genes (26). By microarray analysis, USA300 displayed an increased expression of genes encoding cell envelope proteins (including lipoproteins and superantigen-like proteins), genes residing in the prophage Sa3usa, several genes contained in pathogenicity islands vSA␣ and vSAß, genes encoding proteases, and the gene encoding the IgG binding protein Sbi (26).…”

“…However, USA300 does not contain many more virulence genes than USA400, but it does have an alteration in the expression of regulatory genes and increased expression of certain virulence genes (26). By microarray analysis, USA300 displayed an increased expression of genes encoding cell envelope proteins (including lipoproteins and superantigen-like proteins), genes residing in the prophage Sa3usa, several genes contained in pathogenicity islands vSA␣ and vSAß, genes encoding proteases, and the gene encoding the IgG binding protein Sbi (26). Interestingly our MRSP isolate also had increased expression of several genes, including spsK, which encodes the IgG binding protein Sbi, the toxin genes nucC and coa, prophage genes, and several virulence regulatory genes, including saeRS.…”

Revealing 29 sets of independently modulated genes inStaphylococcus aureus, their regulators and role in key physiological responses

“…However, evidence suggests that this prophage is still active in USA300 strains and its genes are expressed during lung infection, where it may play a role in establishing virulence 57 . Corroborating this hypothesis, we found that the activity of the Phi-Sa3 i-modulon correlated highly with the Vim-3…”