Correlations of mutations in kat G, oxy R- ahp C and inh A genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America

Background Mutations associated with resistance to rifampin or streptomycin have been reported for W/Beijing and Latin American Mediterranean (LAM) strain families of Mycobacterium tuberculosis . A few studies with limited sample sizes have separately evaluated mutations in kat G, ahp C and inh A genes that are associated with isoniazid (INH) resistance. Increasing prevalence of INH resistance, especially in high tuberculosis (TB) prevalent countries is worsening the burden of TB control programs, since similar transmission rates are noted for INH susceptible and resistant M. tuberculosis strains. Results 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 kat G, ahp C and inh A gene loci and correlate with minimal inhibitory concentrations (MIC) levels and spoligotype strain family. Mutations in kat G 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 oxy R- ahp C; inh A regulatory region and inh A structural gene. The S315T kat G mutation was significantly more likely to be associated with MIC for INH ≥2 μg/mL. The S315T kat G mutation was also more frequent in Haarlem family strains than LAM (n = 81) and T strain families. Conclusion Our data suggests that genetic screening for the S315T kat G mutation may provide rapid information for anti-TB regimen selection, epidemiological monitoring of INH resistance and, possibly, to track transmission of INH resistant strains.