title: Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa.
abstract: The Pseudomonas aeruginosa genome contains several different multidrug resistance (MDR) efflux pumps. Overproduction of these pumps reduces susceptibility to a variety of antibiotics. Some recently published works have analyzed the effect of the overproduction of MDR efflux pumps on bacterial virulence. Here we have studied the effect of overproduction of the efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY on type III secretion (T3S) in P. aeruginosa. The type III secretion system (T3SS) is used by P. aeruginosa to deliver toxins directly into the cytoplasm of the host cell. Our data indicate that overexpression of either MexCD-OprJ or MexEF-OprN is associated with the impairment of T3S in P. aeruginosa. No effect on overexpression of either MexAB-OprM or MexXY was detected. The observed defect in T3S was due to a lack of expression of genes belonging to the T3SS regulon. Transcription of this regulon is activated by ExsA in response to environmental signals. Overexpression of this transcriptional regulator complemented the defect in T3S observed in the MexCD-OprJ- and MexEF-OprN-overproducing strains. Taken together, these results suggest that overproduction of either MexCD-OprJ or MexEF-OprN is associated with a reduction in the transcription of the T3SS regulon due to the lack of expression of the exsA gene, encoding the master regulator of the system. The relevance of potential metabolic and quorum-sensing imbalances due to overexpression of MDR pumps associated with this phenotype is also discussed.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Linares
authors.forename: Juan A
authors.initials: JA
authors.lastname: López
authors.forename: Emilio
authors.initials: E
authors.lastname: Camafeita
authors.forename: Juan P
authors.initials: JP
authors.lastname: Albar
authors.forename: Fernando
authors.initials: F
authors.lastname: Rojo
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martínez
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D024901:Drug Resistance, Multiple, Bacterial; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D018085:Regulon; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C095092:ExsA protein, bacteria; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C470189:MexC protein, Pseudomonas aeruginosa; C121980:MexD protein, Pseudomonas aeruginosa; C470190:OprJ protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; C105708:OprN protein, Pseudomonas aeruginosa; D012329:RNA, Bacterial; D012333:RNA, Messenger; D015534:Trans-Activators