Abstract
Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis.
Highlights
Tuberculosis (TB) remains as an important infectious disease and public health concern worldwide.According to the latest World Health Organization (WHO) report, there were an estimated 8.6 million incident cases of TB in 2012 and 1.3 million deaths were attributed to the disease
A more worrying situation has emerged with the description of M. tuberculosis strains that have been found resistant to all antibiotics that were available for testing, a situation labelled as totally drug resistant (TDR)-TB [5,6,7]
Macrolides are more frequently recommended for the treatment of other mycobacterial infections due to their limited activity against M. tuberculosis
Summary
Tuberculosis (TB) remains as an important infectious disease and public health concern worldwide. According to the latest World Health Organization (WHO) report, there were an estimated 8.6 million incident cases of TB in 2012 and 1.3 million deaths were attributed to the disease. MDR-TB is caused by strains of Mycobacterium tuberculosis that are resistant to at least rifampicin and isoniazid, two key drugs in the treatment of the disease. Since 2006, it has been recognized the presence of even more resistant strains of M. tuberculosis labelled as extensively drug resistant (XDR)-TB [2,3,4]. A more worrying situation has emerged with the description of M. tuberculosis strains that have been found resistant to all antibiotics that were available for testing, a situation labelled as totally drug resistant (TDR)-TB [5,6,7]. The following sections will review the mode of action and resistance mechanisms of the main anti-TB drugs as well as new drugs recently described with anti-TB activity
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