Identification of Pseudomonas aeruginosa genes associated with antibiotic susceptibility.

Abstract

Pseudomonas aeruginosa causes acute and chronic infections in humans and these infections are difficult to treat due to the bacteria's high-level of intrinsic and acquired resistance to antibiotics. To address this problem, it is crucial to investigate the molecular mechanisms of antibiotic resistance in this organism. In this study, a P. aeruginosa transposon insertion library of 17000 clones was constructed and screened for altered susceptibility to seven antibiotics. Colonies grown on agar plates containing antibiotics at minimum inhibitory concentrations (MICs) and those unable to grow at 1/2 MIC were collected. The transposon-disrupted genes in 43 confirmed mutants that showed at least a three-fold increase or a two-fold decrease in susceptibility to at least one antibiotic were determined by semi-random PCR and subsequent sequencing analysis. In addition to nine genes known to be associated with antibiotic resistance, including mexI, mexB and mexR, 24 new antibiotic resistance-associated genes were identified, including a fimbrial biogenesis gene pilY1 whose disruption resulted in a 128-fold increase in the MIC of carbenicillin. Twelve of the 43 genes identified were of unknown function. These genes could serve as targets to control or reverse antibiotic resistance in this important human pathogen.

• Authors: Lin Chen, Liang Yang, Xingyan Zhao, Lixin Shen, Kangmin Duan
• Journal: Science China. Life sciences (Sci China Life Sci) Vol. 53 Issue 10 Pg. 1247-51 (Oct 2010) ISSN: 1869-1889 [Electronic] China
• PMID: 20953948 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Drug Resistance, Microbial (genetics)
• Gene Library
• Genes, Bacterial
• Humans
• Microbial Sensitivity Tests
• Mutagenesis, Insertional
• Mutation
• Polymerase Chain Reaction
• Pseudomonas Infections (drug therapy, microbiology)
• Pseudomonas aeruginosa (drug effects, genetics)