Role for nucleotide excision repair in virulence of Mycobacterium tuberculosis.
Mutations in Mycobacterium tuberculosis uvrB result in severe sensitivity to acidified nitrite, a source of nitric oxide (6). In this study, we show that a uvrB mutant is exquisitely sensitive to UV light but not to several sources of reactive oxygen species in vitro. Furthermore, a uvrB mutant was attenuated in mice as judged by an extension of life span. Attenuation in mice was partially reversed by genetic inactivation of nitric oxide synthase 2 (iNOS) and almost completely reversed in mice lacking both iNOS and phagocyte oxidase. Thus, a gene predicted to encode a key element of DNA repair is required for resistance of M. tuberculosis to both reactive nitrogen and reactive oxygen species in mice.
Darwin
K Heran
KH
Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 57, New York, NY 10021, USA.
Nathan
Carl F
CF
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000528:radiation effects; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000528:radiation effects; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays; D014774:Virulence
D001426:Bacterial Proteins; D009573:Nitrites; D017382:Reactive Oxygen Species; D010088:Oxidoreductases; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse