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Chemotherapy In Tuberculosis | Open Access Journals
Cancer Science & Therapy

Cancer Science & Therapy

ISSN: 1948-5956

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Chemotherapy In Tuberculosis

The global effort to fight tuberculosis (TB) is focused on interrupting the transmission of the causative agent, Mycobacterium tuberculosis, through a chemotherapeutic intervention in active infectious diseases. The inadequacy of this approach is manifested by the inexorable annual increase in tuberculosis infection and mortality rates and by the emergence of multidrug-resistant isolates. Critically, the limited effectiveness of the current combination of first-line anti-tuberculosis drugs suggests that the heterogeneity of host and bacillary physiologies could alter the activity of the drug. This review explores the possibility that strategies for adapting M. tuberculosis to hostile in vivo conditions may contribute to the subversion of anti-TB chemotherapy. In particular, the evidence that the infecting bacilli are exposed to immune mediated DNA damage by the environment and the host suggests a role for synthesis of error-prone DNA repair in the generation of mutations in resistance to chromosomally coded antibiotics. The inability of first-line anti-tuberculosis drugs to sterilize a population of sensitive bacilli is, however, independent of genetic resistance and rather involves the functioning of alternative tolerance mechanisms. More specifically, it is proposed that the emergence of persistent subpopulations could depend on the transition to a modified metabolic state induced by the strict alarmone response, (p) ppGpp, possibly involving some or all of the numerous toxin-antitoxin modules identified. in the M. tuberculosis genome.

 

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Citations: 5332

Cancer Science & Therapy received 5332 citations as per Google Scholar report

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