title: Involvement of Holliday junction resolvase in fluoroquinolone-mediated killing of Mycobacterium smegmatis.
abstract: The absence of the Holliday-junction Ruv resolvase of Mycobacterium smegmatis increased the bacteriostatic and bactericidal activities of the fluoroquinolone moxifloxacin, an important antituberculosis agent. The treatment of ruvAB-deficient cells with thiourea and 2,2'-bipyridyl lowered moxifloxacin lethality to wild-type levels, indicating that the absence of ruvAB stimulates a lethal pathway involving reactive oxygen species. A hexapeptide that traps the Holliday junction substrate of RuvAB potentiated moxifloxacin-mediated lethality, supporting the development of small-molecule enhancers for moxifloxacin activity against mycobacteria.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Beibei District, Chongqing, China Second Affiliated Hospital and the Key Laboratory of Molecular Biology of Infectious Diseases of the Ministry of Education, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors.forename: Quanxin
authors.initials: Q
authors.lastname: Long
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Beibei District, Chongqing, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Du
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Beibei District, Chongqing, China.
authors.forename: Tiwei
authors.initials: T
authors.lastname: Fu
authors.affiliation: Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.affiliation: Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang-An District, Xiamen, Fujian Province, China zhaox5@njms.rutgers.edu georgex@swu.edu.cn.
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Beibei District, Chongqing, China zhaox5@njms.rutgers.edu georgex@swu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D045566:DNA, Cruciform / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D024841:Fluoroquinolones / Q000494:pharmacology*; D045565:Holliday Junction Resolvases / Q000378:metabolism*; D000077266:Moxifloxacin; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013890:Thiourea / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D024841:Fluoroquinolones; D017382:Reactive Oxygen Species; D045565:Holliday Junction Resolvases; D013890:Thiourea; D000077266:Moxifloxacin