MRSA epidemic linked to a quickly spreading colonization and virulence determinant

Abstract

The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood1. While a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer2, there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare3,4 mobile genetic element-encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, significantly enhancing nasal colonization, lung disease, and abscess formation, and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type (ST) 239 to invasive clones belonging to other STs. Our study identifies sasX as a quickly spreading critical determinant of MRSA pathogenic success and a promising target for therapeutic interference. Importantly, our results provide proof-of-principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.

Phenotypic and molecular characterization of Staphylococcus aureus recovered from different clinical specimens of inpatients at a teaching hospital in Shanghai between 2005 and 2010

“…Although all ST88 isolates tested in our study were MSSA isolates and were generally susceptible to antibiotics, the infections caused by these isolates should not be ignored. SasX was identified as a quickly spreading crucial determinant of MRSA pathogenic success in a recent study, which also showed that the frequency of the sasX gene among S. aureus and MRSA isolates in China increased from 19-31 % in 2003 to 21-39 % in 2011 (Li et al, 2012). Similarly, the prevalence of the sasX gene in S.…”

“…Adhesin genes (clfA, clfB, cna, fnbA, sdrC, sdrD and sdrE) and other virulence factor genes (icaA and arcA) were amplified according to the method of Campbell et al (2008). The Panton-Valentine leukocidin gene (pvl) and the MRSA-related sasX gene were amplified as described previously by Jarraud et al (2002) and Li et al (2012). Amplification of genes conferring resistance to mupirocin (mupA) and antiseptic (qacA/B) was carried out as described previously by Cadilla et al (2011) and Noguchi et al (2006).…”

Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase

“…S1C). Surface proteins IsdA and SasX are expressed by Chinese MRSA isolates (20). Incubation of affinity-purified IsdA 64-323 (P) or SasX precursor (P) with purified SrtA ΔN24 and NH 2 -Gly 3 nucleophile resulted in sorting signal cleavage to yield the transpeptidation product (M), which could be blocked with the noncompetitive inhibitor N,N,N-trimethyl-2-(methylsulfonylthio)ethanaminium chloride (MTSET) ( Fig.…”

Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria

“…For MRSA, drug resistance is associated with therapeutic failure and increased mortality of human infections (31,32). Glycopeptide (vancomycin) resistance has transferred from enterococci to MRSA (33); the resulting VRSA strains are broadly antibiotic resistant and represent a global infectious threat (34,35). Daptomycin and linezolid have recently been licensed to address the threat of MRSA and VRSA infections (36,37).…”