Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru

Purpose: There is a need for genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates recovered from patients living in areas with a high prevalence of primary and secondary drug resistace to first line antituberculous agents. We investigated the molecular genetics of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains recovered in a Latin American country. Methods: We studied twenty-nine epidemiologically unrelated and mostly MDR-TB strains from Peruvian patients. We determined the antimicrobial agent susceptibility pattern, major genetic group designation, IS6110 fingerprinting, spoligotyping, and automated DNA sequencing of regions of the katG, rpoB, emoB, gyrA, and pncA genes with mutations commonly associated with drug resistance. Results: Nineteen isolates were found to be multidrug-resistant by susceptibility testing. IS6110 typing showed that virtually all isolates were unique and therefore had independently acquired drug resistance. Seventy-nine percent of isoniazid-resistant strains had a Ser315Thr amino acid change in KatG. Ninety-five percent of rifampin-resistant isolates had amino acid replacements in the rifampin-resistance determining region of RpoB. Six of eleven ethambutol-resistant strains had EmbB alterations. Eleven pyrazinamide-resistant strains had distinct mutations in pncA. Conclusions: Virtually all organisms evolved drug resistance independently. The types of drug resistance-associated mutations identified were very similar to changes occurring in isolates from other areas of the world. Clinical Implications: Nucleotide sequence-based strategies for rapid detection of drug resistance-conferring mutants will be applicable to organisms recovered in Peru, and potentially other areas of Latin America.