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

K. Akiba, Tasuke Ando, Emiko Isogai, T. Nakae, Hiroshi Yoneyama

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalChemotherapy
Volume59
Issue number2
DOIs
Publication statusPublished - 2013 Jan 1

Keywords

  • Antibiotic resistance
  • Multidrug efflux pump
  • Outer membrane biogenesis
  • Pseudomonas aeruginosa
  • Screening
  • Tat pathway

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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