Research highlight

Loss of Mycobacterium tuberculosis gene a cause of drug resistance?

Nature Communications

March 21, 2012

Mutations in, or loss of the Sig1 gene may cause Mycobacterium tuberculosis resistance to isoniazid - a drug commonly used to treat tuberculosis. Reported in Nature Communications this week, the findings may have important implications for the drug-resistant forms of this disease. Mutations in Mycobacterium tuberculosis genes following treatment with antibiotics can result in multi-drug resistant and extensively drug resistant forms of the bacteria. These forms of the bacteria can be spread person to person suggesting that resulting strains have sufficient fitness for infection. Isoniazid has been commonly used to treat Mycobacterium tuberculosis but drug resistance is known to results from mutations in the bacterial gene called KatG. This gene is required for the metabolism of isoniazid to form an active intermediate. William Bishai and colleagues now show in the laboratory that loss of another gene that regulates the levels of KatG - Sig1 - also results in resistance to isoniazid and increases death in a mouse model of Mycobacterium tuberculosis. These findings suggest that alterations in Sig1 have the potential to cause drug resistant Mycobacterium tuberculosis.

doi: 10.1038/ncomms1724

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