title: Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa.
abstract: nfxC-type cells of Pseudomonas aeruginosa that produce the MexEF-OprN efflux pump exhibit resistance to fluoroquinolones and chloramphenicol and hypersusceptibility to most classical beta-lactam antibiotics. We investigated the molecular mechanism of how the nfxC mutation causes beta-lactam hypersusceptibility. The MexAB-OprM extrusion pump transports and confers resistance to beta-lactam antibiotics. Interestingly, expression of the mexAB-oprM operon reached the highest level during the mid-stationary growth phase in both wild-type and nfxC-type mutant strains, suggesting that expression of the mexAB-oprM operon may be controlled by cell density-dependent regulation such as quorum sensing. This assumption was verified by demonstrating that exogenous addition of the quorum-sensing autoinducer N-butyryl-L-homoserine lactone (C4-HSL) enhanced the expression of MexAB-OprM, whereas N-(3-oxododecanoyl)-L-homoserine lactone had only a slight effect. Furthermore, this C4-HSL-mediated enhancement of mexAB-oprM expression was repressed by MexT, a positive regulator of the mexEF-oprN operon. It was concluded that beta-lactam hypersusceptibility in nfxC-type mutant cells is caused by MexT-mediated cancellation of C4-HSL-mediated enhancement of MexAB-OprM expression.
authors.affiliation: Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan. maseda@sakura.cc.tsukuba.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Maseda
authors.forename: Isao
authors.initials: I
authors.lastname: Sawada
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroo
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Taiji
authors.initials: T
authors.lastname: Nakae
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nomura
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000235:genetics / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D003227:Conjugation, Genetic / Q000235:genetics; D004274:DNA, Recombinant / Q000096:biosynthesis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009876:Operon / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004274:DNA, Recombinant; D026901:Membrane Transport Proteins; C092312:N-butyrylhomoserine lactone; C402263:OprM protein, Pseudomonas aeruginosa; D015534:Trans-Activators; D015107:4-Butyrolactone