title: Mutation or overexpression of a terminal oxidase leads to a cell division defect and multiple antibiotic sensitivity in Pseudomonas aeruginosa.
abstract: Mutation of the cyanide-insensitive terminal oxidase of Pseudomonas aeruginosa leads to pleiotropic effects. A cio mutant and strains, including the wild-type, carrying the cioAB genes on a multicopy plasmid were temperature-sensitive and had a cell division defect, leading to the formation of non-septate, multinucleated filaments. Such strains of this intrinsically antibiotic-resistant bacterium were more sensitive to a range of antibiotics including chloramphenicol, beta-lactams, quinolones, aminoglycosides, and macrolides. The effect of cio mutation on Deltap-dependent accumulation of chloramphenicol suggested that antibiotic sensitivity resulted from loss of or damage to a multidrug efflux pump. The ability of reducing agents and catalase to suppress the temperature-sensitive phenotype and of catalase to partially suppress antibiotic sensitivity suggested that increased levels of reactive oxygen species might be the cause of the observed phenotypes. Consistent with this was the increased sensitivity of strains to H(2)O(2) and their increased protein carbonyl content, an indicator of oxidative protein modification. The temperature-dependent synthesis of a specific catalase was absent in the cio mutant and in strains carrying multiple plasmid-borne copies of cioAB. We propose that reduced catalase levels result in oxidative modification and consequent loss of function of proteins involved in a range of cellular functions. How mutation or overexpression of the cyanide-insensitive terminal oxidase leads to a loss of catalase activity is unknown at present.
authors.affiliation: Department of Biological Sciences, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, United Kingdom.
authors.forename: Gholam Reza
authors.initials: GR
authors.lastname: Tavankar
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mossialos
authors.forename: Huw D
authors.initials: HD
authors.lastname: Williams
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003486:Cyanides / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D009154:Mutation; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D003486:Cyanides; D010088:Oxidoreductases