“
“Background Tuberculosis (TB) is a global public health problem caused by an infection with Mycobacterium tuberculosis. There were approximately 9 million new cases of TB and 1.3 million deaths in 2012 [1]. The emergence of multidrug-resistant TB (MDR-TB; resistance at least to isoniazid and rifampicin) and extensively drug-resistant TB (XDR-TB; MDR-TB plus resistance to any fluoroquinolones and one of the CRM1 inhibitor second-line injectable drugs, amikacin, kanamycin and capreomycin) remains a global health problem that hinders the prevention, treatment, and control of TB. In

Thailand, approximately 80,000 new TB cases were notified in 2012 and MDR-TB appeared in 1.7% and 35% of new TB cases and previously treated TB cases, respectively [1]. Rapid identification of drug-resistant strains is one of the major strategies for fighting against TB. Molecular-based methods for detection of drug resistance genes have been shown to be a promising method for identification of drug-resistant Selleckchem Fedratinib strains; for example, the

Xpert MTB/RIF assay and the GenoType MTBDRplus assay have been successfully used to identify rifampicin-resistant M. tuberculosis and MDR-TB, respectively [2–7]. In contrast, knowledge concerning resistance Quisinostat chemical structure mechanisms of the second-line anti-TB drugs is still limited. Better understanding of the resistance mechanisms of these drugs could lead to the development of a high sensitive test for detection of the resistance genes and also promote the use of molecular-based methods for screening the strains resistant to second-line drugs, including the XDR-TB strain. The aminoglycosides amikacin (AK) and kanamycin (KM) are the second-line

injectable drugs used to treat MDR-TB. The drugs bind to 16S rRNA in the 30S small ribosomal subunit and inhibit protein synthesis [8]. Mutations in the rrs gene encoding 16S rRNA are associated with high-level drug resistance in M. tuberculosis; the rrs A1401G mutation is the most frequently reported mutation and has been identified in 30 to 90% of KM-resistant M. tuberculosis strains [9–12]. Recently, overexpression of the aminoglycoside acetyltransferase-encoding gene, eis, has been associated with a low-level resistance to KM [13, 14]. This overexpression resulted from either point mutations in the promoter region of the eis gene or mutations in the 5′ untranslated region (UTR) click here of the whiB7 gene, which encodes a putative regulator of the eis gene. This type of eis promoter mutation was found in 26-80% of KM-resistant M. tuberculosis clinical strains [14–17]. However, some resistant strains do not contain any known mutations. Other possible resistance mechanisms, including the presence of drug efflux pumps or enzymes that can inactivate the drug or modify the drug target, have been proposed. Tap, a putative efflux pump that was originally described in Mycobacterium fortuitum, conferred resistance to tetracycline and aminoglycosides when introduced into M. smegmatis [18].