title: Comparative proteomics-based identification of genes associated with glycopeptide resistance in clinically derived heterogeneous vancomycin-intermediate Staphylococcus aureus strains.
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.
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Chen
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Zhao
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.forename: Minjun
authors.initials: M
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome; D014640:Vancomycin