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Nitrite impacts the survival of Mycobacterium tuberculosis in response to isoniazid and hydrogen peroxide
Author(s) -
CunninghamBussel Amy,
Bange Franz C.,
Nathan Carl F.
Publication year - 2013
Publication title -
microbiologyopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.881
H-Index - 36
ISSN - 2045-8827
DOI - 10.1002/mbo3.126
Subject(s) - isoniazid , hydrogen peroxide , mycobacterium tuberculosis , tuberculosis , nitrite , microbiology and biotechnology , medicine , chemistry , biology , nitrate , pathology , organic chemistry
When access to molecular oxygen is restricted, Mycobacterium tuberculosis (Mtb) can respire an alternative electron acceptor, nitrate. We found that Mtb within infected primary human macrophages in vitro at physiologic tissue oxygen tensions respired nitrate, generating copious nitrite. A strain of Mtb lacking a functioning nitrate reductase was more susceptible than wild‐type Mtb to treatment with isoniazid during infection of macrophages. Likewise, nitrate reductase‐deficient Mtb was more susceptible to isoniazid than wild‐type Mtb in axenic culture, and more resistant to hydrogen peroxide. These phenotypes were reversed by the addition of exogenous nitrite. Further investigation suggested that nitrite might inhibit the bacterial catalase. To the extent that Mtb itself is the most relevant source of nitrite acting within Mtb, these findings suggest that inhibitors of Mtb's nitrate transporter or nitrate reductase could enhance the efficacy of isoniazid.

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