title: Efficacy of AiiM, an N-acylhomoserine lactonase, against Pseudomonas aeruginosa in a mouse model of acute pneumonia.
abstract: Quorum sensing (QS) in Pseudomonas aeruginosa regulates the production of many virulence factors and plays an important role in the pathogenesis of P. aeruginosa infection. N-acyl homoserine lactones (AHL) are major QS signal molecules. Recently, a novel AHL-lactonase enzyme, AiiM, has been identified. The aim of this study was to evaluate the effect of AiiM on the virulence of P. aeruginosa in a mouse model of acute pneumonia. We developed a P. aeruginosa PAO1 strain harboring an AiiM-expressing plasmid. The production of several virulence factors by the AiiM-expressing strain was examined. Mice were intratracheally infected with an AiiM-expressing PAO1 strain. Lung histopathology, bacterial burden, and bronchoalveolar lavage (BAL) fluid were assessed at 24 h postinfection. AiiM expression in PAO1 reduced production of AHL-mediated virulence factors and attenuated cytotoxicity against human lung epithelial cells. In a mouse model of acute pneumonia, AiiM expression reduced lung injury and greatly improved the survival rates. The levels of proinflammatory cytokines and myeloperoxidase activity in BAL fluid were significantly lower in mice infected with AiiM-expressing PAO1. Thus, AiiM can strongly attenuate P. aeruginosa virulence in a mammalian model and is a potential candidate for use as a therapeutic agent against P. aeruginosa infection.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Migiyama
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morohoshi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Taiga
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeya
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D010196:Pancreatic Elastase / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000473:pathology / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000472:pathogenicity*; D011710:Pyocyanine / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing; D016019:Survival Analysis; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D007378:Interleukins; D037521:Virulence Factors; D011710:Pyocyanine; D009195:Peroxidase; D002265:Carboxylic Ester Hydrolases; C432003:N-acyl homoserine lactonase; D010196:Pancreatic Elastase