Abstract
Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is associated with clinical treatment failure. However, the resistance mechanism of hVISA has not been fully clarified. In the present study, comparative proteomics analysis of two pairs of isogenic vancomycin-susceptible S. aureus (VSSA) and hVISA strains isolated from two patients identified five differentially expressed proteins, IsaA, MsrA2, Asp23, GpmA, and AhpC, present in both isolate pairs. All the proteins were up-regulated in the hVISA strains. These proteins were analyzed in six pairs of isogenic VSSA and hVISA strains, and unrelated VSSA (n = 30) and hVISA (n = 24) by real-time quantitative reverse transcriptase–PCR (qRT–PCR). Of the six pairs of isogenic strains, isaA, msrA2 and ahpC were up-regulated in all six hVISA strains; whereas asp23 and gpmA were up-regulated in five hVISA strains compared with the VSSA parental strains. In the unrelated strains, statistical analyses showed that only isaA was significantly up-regulated in the hVISA strains. Analysis of the five differentially expressed proteins in 15 pairs of persistent VSSA strains by qRT–PCR showed no differences in the expression of the five genes among the persistent strains, suggesting that these genes are not associated with persistence infection. Our results indicate that increased expression of isaA may be related to hVISA resistance.
Highlights
Staphylococcus aureus can cause serious hospital- and communityacquired infections, including skin and soft tissue infections, pneumonia, bacteremia, endocarditis, and even septic shock
Genotypic Characterization of the Isolate Set Two pairs of isogenic vancomycin-susceptible S. aureus (VSSA) and Heterogeneous vancomycin-intermediate resistant S. aureus (hVISA) isolates that belonged to SCCmecIII-ST239-spa t030 were selected for the comparative proteomics analysis to minimize variation unrelated to the vancomycin resistance phenotype
The results showed that isaA, msrA2, and ahpC were up-regulated in all six hVISA strains, whereas asp23 and gpmA were up-regulated in five hVISA strains compared with the VSSA parental strain
Summary
Staphylococcus aureus can cause serious hospital- and communityacquired infections, including skin and soft tissue infections, pneumonia, bacteremia, endocarditis, and even septic shock. The high prevalence of methicillin-resistant S. aureus (MRSA) and the extensive use of vancomycin have led to the emergence of reduced vancomycin susceptibility among S. aureus strains. Vancomycin-resistant S. aureus (VRSA) strains are rare, hVISA/VISA are common in the clinical setting, especially in persistent MRSA bacteremia and endocarditis. Our previous studies have shown that the prevalence of hVISA is 13% to 16% in large teaching hospitals in China [1]. Several studies have indicated that hVISA/VISA infections are associated with vancomycin treatment failure [2,3]
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