title: VraR Binding to the Promoter Region ofagrInhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.
abstract: Acquisition of vancomycin resistance inStaphylococcus aureusis often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediateS. aureus(hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene (vraR) and decreased expression of virulence genes (hla,hlb, andcoa) and virulence-regulated genes (RNAIII,agrA, andsaeR). These results suggested that VraR might have a direct or indirect effect on virulence inS. aureusIn electrophoretic mobility shift assays, VraR did not bind to promoter sequences ofhla,hlb, andcoagenes, but it did bind to theagrpromoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between theagrP2 and P3 promoters. These results indicated that whenS. aureusis subject to induction by vancomycin, expression ofvraRis upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR inS. aureusis involved not only in the regulation of vancomycin resistance but also in the regulation of virulence.
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Liangfei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Huaiwei
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China xiaolingma@126.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000096:biosynthesis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053038:Quorum Sensing / Q000187:drug effects; D012329:RNA, Bacterial / Q000096:biosynthesis; D013108:Sphingomyelin Phosphodiesterase / Q000096:biosynthesis; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000235:genetics*; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D006460:Hemolysin Proteins; C109237:OmpF protein; D018272:Porins; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; C433805:SaeR protein, Staphylococcus aureus; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; C478170:VraR protein, Staphylococcus aureus; C478169:VraS protein, Staphylococcus aureus; C021091:staphylococcal alpha-toxin; D014640:Vancomycin; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus
keywords: Staphylococcus aureus; global regulatory networks; two-component regulatory systems; vancomycin resistance; virulence regulation