Abstract
A search to identify new mechanisms of isoniazid resistance in Mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (mshA) or the cysteine ligase (mshC). These mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. This study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial species.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antitubercular Agents / pharmacology*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Carbon-Sulfur Lyases / genetics
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Carbon-Sulfur Lyases / metabolism
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Cysteine / biosynthesis
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Cysteine / genetics*
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Drug Resistance, Bacterial / genetics
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Ethionamide / pharmacology*
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Glycopeptides / biosynthesis
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Glycopeptides / genetics*
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Glycosyltransferases / genetics
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Glycosyltransferases / metabolism
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Inositol / biosynthesis
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Inositol / genetics*
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Isoniazid / pharmacology*
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Mycobacterium bovis / drug effects*
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Mycobacterium bovis / genetics*
Substances
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Antitubercular Agents
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Bacterial Proteins
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Glycopeptides
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mycothiol
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Inositol
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Glycosyltransferases
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Carbon-Sulfur Lyases
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cysteine lyase
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Cysteine
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Ethionamide
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Isoniazid