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
Elis R Dalla Costa, Marta O Ribeiro, Márcia SN Silva, Liane S Arnold, Diana C Rostirolla, Patricia I Cafrune, Roger C Espinoza, Moises Palaci, Maria A Telles, Viviana Ritacco, Philip N Suffys, Maria L Lopes, Creuza L Campelo, Silvana S Miranda, Kristin Kremer, Pedro E Almeida da Silva, Leila de Souza Fonseca, John L Ho, Afrânio L Kritski and Maria LR Rossetti
ABSTRACT
Background
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 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.
Conclusion
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.