期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 61, 期 12, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01596-17
关键词
Mycobacterium tuberculosis; persistence; sigma factors
资金
- European Community's Seventh Framework Programme [260872]
The emergence and spread of drug-resistant Mycobacterium tuberculosis strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of M. tuberculosis (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for M. tuberculosis mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce M. tuberculosis virulence in vivo but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing.
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