Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bacterial Proteins / genetics*
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Bacterial Proteins / metabolism
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DNA Repair* / radiation effects
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Macrophages / microbiology
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Mice
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Mutation
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / metabolism
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Mycobacterium tuberculosis / pathogenicity*
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Mycobacterium tuberculosis / radiation effects
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Nitrites / metabolism
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Oxidoreductases / genetics
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Oxidoreductases / metabolism
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Reactive Oxygen Species / metabolism
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Ultraviolet Rays
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Virulence
Substances
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Bacterial Proteins
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Nitrites
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Reactive Oxygen Species
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Oxidoreductases
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse