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Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America

DOI: 10.1186/1471-2180-9-39

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Abstract:

We, therefore, conducted a comprehensive evaluation of INH resistant M. tuberculosis strains (n = 224) from three South American countries with high burden of drug resistant TB to characterize mutations in katG, ahpC and inhA gene loci and correlate with minimal inhibitory concentrations (MIC) levels and spoligotype strain family. Mutations in katG were observed in 181 (80.8%) of the isolates of which 178 (98.3%) was contributed by the katG S315T mutation. Additional mutations seen included oxyR-ahpC; inhA regulatory region and inhA structural gene. The S315T katG mutation was significantly more likely to be associated with MIC for INH ≥2 μg/mL. The S315T katG mutation was also more frequent in Haarlem family strains than LAM (n = 81) and T strain families.Our data suggests that genetic screening for the S315T katG mutation may provide rapid information for anti-TB regimen selection, epidemiological monitoring of INH resistance and, possibly, to track transmission of INH resistant strains.Tuberculosis (TB), a curable disease caused by M. tuberculosis, has never been adequately controlled in high prevalence countries because of inadequate funding of public health programs and limited access to health care caused by poverty. In the last several decades, the concurrent HIV epidemic has further accentuated the magnitude of the global TB burden. Further complicating the TB resurgence is the recent increase in the occurrence of simultaneous resistance to first line drugs, isoniazid (INH) and rifampin (RIF), that defines multidrug resistance (MDR), as well as, to second line drugs, resulting in extensive drug resistance (XDR) [1,2]. Although current control measures and short-term treatment schemes address the problem of drug resistance, knowledge on individual drug resistance profiles is needed for targeted intervention [3]. Global surveillance of M. tuberculosis drug resistance has been proposed to guide appropriate treatment policies [4]. Brazil and Peru are responsible

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