title: RND type efflux pump system MexAB-OprM of Pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication.
abstract: BACKGROUND
  Bacteria release a wide variety of small molecules including cell-to-cell signaling compounds. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl-HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. QS plays a significant role in the pathogenesis of infectious diseases and in beneficial symbiosis by responding to acyl-HSLs in Pseudomonas aeruginosa. It is considered that the selection of bacterial languages is necessary to regulate gene expression and thus it leads to the regulation of virulence and provides a growth advantage in several environments. In this study, we hypothesized that RND-type efflux pump system MexAB-OprM of P. aeruginosa might function in the selection of acyl-HSLs, and we provide evidence to support this hypothesis.
  
  
  RESULTS
  Loss of MexAB-OprM due to deletion of mexB caused increases in QS responses, as shown by the expression of gfp located downstream of the lasB promoter and LasB elastase activity, which is regulated by a LasR-3-oxo-C12-HSL complex. Either complementation with a plasmid containing wild-type mexB or the addition of a LasR-specific inhibitor, patulin, repressed these high responses to 3-oxo-acyl-HSLs. Furthermore, it was shown that the acyl-HSLs-dependent response of P. aeruginosa was affected by the inhibition of MexB transport activity and the mexB mutant. The P. aeruginosa MexAB-OprM deletion mutant showed a strong QS response to 3-oxo-C10-HSL produced by Vibrio anguillarum in a bacterial cross-talk experiment.
  
  
  CONCLUSIONS
  This work demonstrated that MexAB-OprM does not control the binding of LasR to 3-oxo-Cn-HSLs but rather accessibility of non-cognate acyl-HSLs to LasR in P. aeruginosa. MexAB-OprM not only influences multidrug resistance, but also selects acyl-HSLs and regulates QS in P. aeruginosa. The results demonstrate a new QS regulation mechanism via the efflux system MexAB-OprM in P. aeruginosa.
authors.affiliation: Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Minagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inami
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kato
authors.forename: Shinji
authors.initials: S
authors.lastname: Sawada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yasuki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyairi
authors.forename: Manabu
authors.initials: M
authors.lastname: Horikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Okuda
authors.forename: Naomasa
authors.initials: N
authors.lastname: Gotoh
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D007783:Lactones / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053038:Quorum Sensing; D015398:Signal Transduction; D014733:Vibrio / Q000378:metabolism / Q000502:physiology
chemical_list: D054742:Acyl-Butyrolactones; D001425:Bacterial Outer Membrane Proteins; D007783:Lactones; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D049452:Green Fluorescent Proteins; C085113:Pseudomonas aeruginosa autoinducer; D006714:Homoserine