Isoniazid resistance without a loss of fitness in Mycobacterium tuberculosis
نویسندگان
چکیده
The emergence of multi- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) has intensified the critical public health implications of this global disease. The fitness of Mycobacterium tuberculosis (M.tb.) strains exhibiting MDR and XDR phenotypes is of fundamental importance in predicting whether the MDR-/XDR-TB epidemic will be sustained across the human population. Here we describe a potential mechanism of M.tb. resistance to the TB drug isoniazid (INH) conferred by loss of a sigma factor, SigI. We demonstrate that the gain of INH resistance in the M.tb. ΔsigI mutant might not diminish the organism's fitness for causing disease. These findings have significant implications when considering the ability of drug-resistant M.tb. strains to initiate untreatable TB epidemics, as it is possible that loss or alteration of SigI function could have a role in the generation of MDR and XDR M.tb. strains of suitable fitness to spread in a community setting.
منابع مشابه
Minor Contribution of inhA-15 Mutations to the Rapid Detection of Isoniazid Resistance in Mycobacterium Tuberculosis Isolates
متن کامل
Isoniazid MIC and KatG Gene Mutations among Mycobacterium tuberculosis Isolates in Northwest of Iran
Objective(s) Isoniazid (INH) is one of the main first line drugs used in treatment of tuberculosis and development of resistance against this compound can result in serious problems in treatment procedures. Resistance to INH is mediated mainly by mutation in KatG gene that is coded for the catalase enzyme. The proportional method for detection of INH-resistance is time consuming due to the slo...
متن کاملDetection of Isoniazid and Rifampin Resistant Strain of Mycobacterium Tuberculosis Isolated from patients in Golestan province (North of Iran)
Abstract Background and objectives: With almost nine million new cases each year, tuberculosis is still one of the most Life-threatening diseases in the World. Distribution of drug resistant strains of M.tuberculosis has a lot of importance. This research was carried out to determine the frequency of drug resistance of M. tuberculosis in strains isolated in Golestan province. Material and...
متن کاملEvaluating the effect of Dracocephalum kotschyi methanol extract on Mycobacterium tuberculosis
Background and objectives: Tuberculosis (TB) is the major public health problem in the world. Each year there are 2-3 million deaths worldwide caused by TB. The increasing incidence of Multi Drug Resistance tuberculosis (MDR-TB) worldwide highlights the urgent need to search for new anti-tuberculosis compounds. It has been reported that medicinal plant, Dracocephalum kotschyi, possesse...
متن کاملتشخیص موتاسیون در کدون 315 ژن katG، مارکر مقاومت به ایزونیازید در سوشهای مایکوباکتریوم توبرکولوزیس جدا شده از بیماران اصفهان و تهران با روش PCR-RFLP
Background and Objective: Drug resistance to tuberculosis is continuously increasing and is a significant threat to tuberculosis control programs because afew effective drugs are present against Mycobacterium tuberculosis. Although isoniazid (INH) is the most effective drug against tuberculosis, resistance to this drug also develops readily. Mutations in katG, specially the Ser315Thr substituti...
متن کامل