Subunit swapping in the Mex-extrusion pumps in Pseudomonas aeruginosa

Hiroshi Yoneyama, Aydin Ocaktan, Naomasa Gotoh, Takeshi Nishino, Taiji Nakae

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Pseudomonas aeruginosa encodes three sets of antibiotic extrusion proteins designated as MexA,B-OprM, MexC,D-OprJ and MexE,F-OprN regulated by the nalB, nfxB and nfxC genes, respectively. MexB,D,F, OprM,J,N and MexA,C,E function as the inner membrane pumps, the outer membrane channels and the membrane fusion proteins, respectively. To investigate the possibility of subunit interchangeabilities, we constructed the following combinations of chimeric pumps: MexA,D-OprM/ΔMexB, MexC,B-OprM/ΔMexA, and MexA,B-OprJ/ΔOprM. The strains producing MexA,D-OprM/ΔMexB and MexC,B-OprM/ΔMexA failed to restore the antibiotic resistance shown in the strains producing the natural combinations of the subunit proteins. These results suggested that the inner membrane components cannot be interchanged. In contrast, the stains producing MexA,B-OprJ/ΔOprM exhibited higher resistance to several antibiotics than the mutant lacking OprM and lower resistance than the strain overexpressing OprM. This result suggests that OprJ may complement the OprM function partially. A spectrum of antibiotics, of which the minimum inhibitory concentrations were restored partially by the complementation, was the same as the spectrum to which the nalB type mutant shows resistance. We surmised from these results that the MexA/MexB unit sustains the substrate specificity of the MexA,B-OprM machinery.

Original languageEnglish
Pages (from-to)898-902
Number of pages5
JournalBiochemical and biophysical research communications
Volume244
Issue number3
DOIs
Publication statusPublished - 1998 Mar 27
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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