Characterization of pncA gene mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from Mexico

Numerous studies have linked mutations in the pncA gene with resistance to pyrazinamide (Z) in Mycobacterium tuberculosis. However, variations in these mutations are specific to the country of origin of the isolate. The aim of this study was to characterize changes in pncA gene sequence in isolates of M. tuberculosis with resistance to Z, from patients in Mexico. M. tuberculosis isolates were recovered from individuals suspected of carrying drug resistant tuberculosis and respective susceptibility tests were developed. In isolates with resistance to pyrazinamide the pncA gene and its promoter were analyzed by capillary sequencing. From 127 drug-resistant isolates collected, 42 (33%) were resistant to pyrazinamide. The pncA sequences showed 26 changes in 34 (81%) isolates: 18 SNPs (n=26, 62%), four insertions (n=4, 9.5%) and four deletions (n=4, 9.5%). Absence of modifications was observed in eight (19%) sequences/isolates. The most frequent changes were the mutations L120P (n=7) and K96R (n=4). Twelve changes found are reported for the first time. This is the first description of pncA gene modifications in pyrazinamide resistant isolates originating in Mexico. We conclude that the diversity of changes in pncA indicates the presence of a noteworthy variety of pyrazinamide resistant strains occurring in the area.