title: Functional analysis of spoT, relA and dksA genes on quinolone tolerance in Pseudomonas aeruginosa under nongrowing condition.
abstract: To assess the contribution of ppGpp in antibiotic tolerance to quinolone in Pseudomonas aeruginosa, knockout mutants of the genes involved or linked with the stringent response, such as relA, spoT and dksA, were constructed and investigated for their antibiotic susceptibility to quinolones. The survival of the dksA and spoT mutants in the presence of 8 microg/ml of ofloxacin and 1 microg/ml of ciprofloxacin were shown to be approximately 20-180 and 10-40 times respectively, higher than the same for the wild type strain. The intracellular levels of ppGpp determined with high performance liquid chromatography (HPLC) demonstrated that spoT and dksA mutants possess higher basal levels of ppGpp. The data suggest that elevated basal levels of ppGpp may be responsible for rendering these mutants tolerant to quinolones and expand the importance of ppGpp as an antimicrobial target in P. aeruginosa.
authors.affiliation: Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Darija
authors.initials: D
authors.lastname: Viducic
authors.forename: Tsuneko
authors.initials: T
authors.lastname: Ono
authors.forename: Keiji
authors.initials: K
authors.lastname: Murakami
authors.forename: Heni
authors.initials: H
authors.lastname: Susilowati
authors.forename: Shizuo
authors.initials: S
authors.lastname: Kayama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hirota
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Miyake
mesh_terms: D002939:Ciprofloxacin / Q000494:pharmacology; D004351:Drug Resistance; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D015363:Quinolones; D006159:Guanosine Tetraphosphate; D002939:Ciprofloxacin; D015242:Ofloxacin