Identification and characterization of an organic solvent tolerance gene in Helicobacter pylori

Helicobacter. 2007 Feb;12(1):74-81. doi: 10.1111/j.1523-5378.2007.00473.x.

Abstract

Background: Pre-cleaning and soaking in glutaraldehyde is the necessary procedure to disinfect endoscopes. However, some chemical-solvent-tolerant bacteria may survive after incomplete endoscopic disinfection. The goal of this study was to identify glutaraldehyde resistance-related genes in Helicobacter pylori.

Materials and methods: Lambda-Zap phagemid expression library of H. pylori strain NTUH-C1 was selected with 0.1% glutaraldehyde. The minimal inhibitory concentration (MIC) of glutaraldehyde-resistant DNA fragments of H. pylori NTUH-C1 strain were determined. Imp/OstA recombinant protein was expressed, purified, and used to generate anti-Imp/OstA polyclonal antibody. Imp/ostA knockout, deletion, and complementation strains were constructed. The function of Imp/OstA was monitored by organic solvent tolerance assay, antibiotics susceptibility test, and N-phenylnapthylamine assay.

Results: Using Imp/ostA polyclonal antibody against cell lysate of wild-type and imp/ostA mutant showed that it is not essential in H. pylori. Organic solvent tolerance assay demonstrated the role of Imp/ostA in n-hexane tolerance. MIC test showed that the mutation of imp/ostA was susceptible to hydrophobic and beta-lactam antibiotics. NPN assay demonstrated that the level of outer membrane permeability was increased by 50% in mutant strain comparing to wild-type strain (p < .001).

Conclusions: We have identified an Imp/OstA protein that was associated with glutaraldehyde resistance in our clinical strain H. pylori NTUH-C1 by screening of lambda-Zap expression library. Disruption of this protein results in altering membrane permeability, sensitivity to organic solvent, and susceptibility to antibiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics*
  • Disinfectants / pharmacology*
  • Drug Resistance / genetics
  • Endoscopy / adverse effects
  • Gene Deletion
  • Genes, Bacterial / physiology
  • Glutaral / pharmacology*
  • Helicobacter Infections / etiology
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / genetics*
  • Hexanes / pharmacology
  • Inosine Monophosphate
  • Microbial Sensitivity Tests

Substances

  • Bacterial Outer Membrane Proteins
  • Disinfectants
  • Hexanes
  • Inosine Monophosphate
  • n-hexane
  • Glutaral