Editors' ChoiceTuberculosis

Understanding Drug Resistance in Tuberculosis

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Science Translational Medicine  18 Nov 2009:
Vol. 1, Issue 7, pp. 7ec27
DOI: 10.1126/scitranslmed.3000610

Tuberculosis (TB) is among the world's deadliest diseases. According to the World Health Organization, it resulted in nearly 1.8 million deaths worldwide in 2007. Caused by the bacterium Mycobacterium tuberculosis, TB is generally curable with anti-TB drugs. Because of misuse or mismanagement of these drugs, however, multidrug-resistant strains of TB have emerged that require extended treatment with second-line anti-TB drugs like kanamycin and amikacin. Extensively drug-resistant TB is also resistant to one or both of these second-line drugs, further limiting effective treatment options. Knowledge of the drug-resistance profile of a patient’s particular bacterial isolate can aid in the choice of drugs and help prevent additional drug resistances from arising. Especially in developing countries where culture facilities are limited, diagnosis of an isolate's resistance profile with molecular biological techniques is a useful approach, but relatively little is known about the molecular basis of resistance to second-line anti-TB drugs. To gain a better understanding of this issue, Zaunbrecher et al. sought to determine the mechanism of low-level kanamycin resistance in M. tuberculosis. These researchers identified mutations in the promoter region of the eis gene, which increase Eis protein levels, conferring resistance to kanamycin. The mutations were present in 80% of the clinical isolates with low-level kanamycin resistance analyzed in this study. Although it is often assumed that isolates that are resistant to kanamycin are also resistant to amikacin, the eis promoter mutations did not confer resistance to amikacin. Thus, the presence of eis mutations might help identify strains that could be usefully treated with amikacin.

M. A. Zaunbrecher et al., Overexpression of the chromosomally encoded aminoglycoside acetytransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc. Nat. Acad. Sci. U.S.A. 11 November 2009 (10.1073/pnas.0907925106) [Full Text]

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