title: Development of ceftriaxone resistance affects the virulence properties of Salmonella enterica serotype Typhimurium strains.
abstract: Development of antibiotic resistance may alter the virulence properties of bacterial organisms. In this study, nine clinical ceftriaxone-susceptible Salmonella enterica serotype Typhimurium strains were subjected to stepwise selection with increasing concentrations of ceftriaxone in culture media. Mutations in virulence-associated genes and antibiotic efflux genes were analyzed by polymerase chain reaction (PCR) and DNA sequencing. The expression levels of virulence genes invA and stn as well as efflux pump genes tolC, arcA, and arcB before and after the selection were measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The stepwise selection resulted in the development of Salmonella strains that were highly resistant to ceftriaxone. Sequence analysis did not reveal any mutations or deletions in the examined virulence genes and regulatory gene, but a silent mutation (T423C) in acrR (encoding a repressor for the efflux pump) was detected in most of the ceftriaxone-resistant strains. The qRT-PCR revealed increased expression of the AcrAB-TolC efflux pump and decreased expression of invA and stn in the ceftriaxone-resistant strains. Moreover, decreased invasion into cultured epithelial cells and reduced growth rates were observed with the resistant strains. These results suggest that acquisition of ceftriaxone resistance is associated with the overexpression of the AcrAB-TolC efflux pump and leads to reduced virulence in Salmonella Typhimurium.
authors: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors: Liang
authors: L
authors: Li
authors: Yu-Rong
authors: YR
authors: Yang
authors: Xiao-Ping
authors: XP
authors: Liao
authors: Chun-Yin
authors: CY
authors: Lei
authors: Jian
authors: J
authors: Sun
authors: Lu-Lu
authors: LL
authors: Li
authors: Bao-Tao
authors: BT
authors: Liu
authors: Shou-Shen
authors: SS
authors: Yang
authors: Ya-Hong
authors: YH
authors: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002443:Ceftriaxone / Q000494:pharmacology*; D018550:Cephalosporin Resistance / Q000235:genetics*; D015536:Down-Regulation; D004768:Enterotoxins / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017354:Point Mutation; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D012480:Salmonella Infections / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D017422:Sequence Analysis, DNA; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C041610:arcA protein, E coli; C082864:enterotoxin, Salmonella; C075518:invA protein, Bacteria; D002443:Ceftriaxone