title: MexT modulates virulence determinants in Pseudomonas aeruginosa independent of the MexEF-OprN efflux pump.
abstract: In the human pathogen Pseudomonas aeruginosa, the LysR-family regulator MexT modulates the induction of the tripartite MexEF-OprN resistance nodulation-division multi-drug efflux system resulting in increased resistance to diverse antibiotics. The MexEF-OprN system is normally quiescent in wild-type cells, but is highly induced in nfxC-type phenotypic mutants in a MexT dependent manner. In addition to antibiotic resistance, induction of mexEF-oprN in nfxC-type mutants has been linked to reduced levels of homoserine lactone-dependent virulence traits, including pyocyanin, elastase, rhamnolipids and PQS and to reduced expression of type three secretion effector proteins. In this study, MexT is overexpressed in wild-type PAO1 and an isogenic mexEF deletion mutant to determine if MexT regulates diverse virulence phenotypes dependent or independent of MexEF-OprN. It is shown that MexT regulates type three secretion, pyocyanin production and early surface attachment independent of MexEF-OprN. In contrast, MexT modulation of the expression of the virulence genes rhlA, lasB and hcnB is dependent on MexEF-OprN, which apparently mediates these effects via efflux of cell-signaling intermediates. The data presented demonstrates that MexT may play a more global role in modulating P. aeruginosa virulence than previously reported and suggests that MexT regulates diverse targets that mediate phenotypic alterations independent of MexEF-OprN.
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Zhe-Xian
authors.initials: ZX
authors.lastname: Tian
authors.forename: Micheál
authors.initials: M
authors.lastname: Mac Aogáin
authors.forename: Hazel F
authors.initials: HF
authors.lastname: O'Connor
authors.forename: Emilie
authors.initials: E
authors.lastname: Fargier
authors.forename: Marlies J
authors.initials: MJ
authors.lastname: Mooij
authors.forename: Claire
authors.initials: C
authors.lastname: Adams
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
mesh_terms: D001422:Bacterial Adhesion; D017353:Gene Deletion; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011709:Pyocins / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D026901:Membrane Transport Proteins; D011709:Pyocins; D014157:Transcription Factors; D037521:Virulence Factors