Tat pathway-mediated translocation of the Sec pathway substrate OprM, an outer membrane subunit of the resistance nodulation division xenobiotic extrusion pumps, in Pseudomonas Aeruginosa

Chemotherapy. 2013;59(2):129-37. doi: 10.1159/000353894. Epub 2013 Sep 18.

Abstract

Background: Pseudomonas aeruginosa produces the Sec and Tat protein secretion machineries. The latter appears to be involved in the secretion of virulence factors, including phospholipase C (PlcH), and hence is a potential target of chemotherapeutic agents.

Methods: The signal sequence of OprM, the outer membrane subunit of the xenobiotic extrusion pumps, was substituted with that of PlcH. The antibiotic susceptibility of oprM-deficient cells expressing the hybrid protein PlcH-OprM was evaluated using the agar dilution method.

Results: The PlcH-OprM-expressing cells showed resistance to various MexAB-OprM substrate antibiotics. To evaluate the translocation route of PlcH-OprM, tatC encoding an indispensable component of the Tat machinery was knocked out in oprM-deficient cells. The tatC-oprM double mutant expressing PlcH-OprM exhibited antibiotic hypersusceptibility like the oprM-deficient cells, indicating that PlcH-OprM was translocated across the inner membrane exclusively through the Tat system.

Conclusions: This system can be used for the screening of Tat system inhibitors and will be an excellent model for the study of secretion and biogenesis of the β-barrel outer membrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial / drug effects
  • Membrane Transport Proteins / deficiency
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / metabolism
  • SEC Translocation Channels
  • SecA Proteins
  • Substrate Specificity
  • Xenobiotics / metabolism
  • Xenobiotics / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Membrane Transport Proteins
  • OprM protein, Pseudomonas aeruginosa
  • SEC Translocation Channels
  • Xenobiotics
  • Adenosine Triphosphatases
  • SecA Proteins