Characterization of pncA mutations of pyrazinamide-resistant Mycobacteriumtuberculosis in Korea

Pyrazinamide (PZA) is one of the most important drugs for the treatment of Mycobacterium tuberculosis infection. However, the increasing frequency of PZA-resistant strains limits its effectiveness. in Korea, most PZA-resistan t strains also exhibit both isoniazid and rifampin resistance making it ess ential to identify these resistant strains accurately and rapidly for effec tive treatment of mycobacterial infection. In this study, the characteristi cs and frequency of mutations of the pncA gene encoding pyrazinamidase were investigated in PZA-resistant clinical isolates from Korea. Automated DNA sequencing was used to evaluate the usefulness of DNA-based detection of PZ A resistance. Among 95 PZA-resistant clinical isolates, 92 (97%) exhibited mutations potentially affecting either the production or the activity of th e enzyme. Mutations were found throughout the pncA gene including the upstr eam region. Single nucleotide replacement appeared to be the major mutation al event (69/92), although multiple substitutions as well as insertion and deletion of nucleotides were also identified. The high frequency of pncA mu tations observed in this study supports the usefulness of DNA-based detecti on of PZA-resistant M. tuberculosis, Having verified the scattered and dive rse mutational characteristics of the pncA gene, automated DNA sequencing s eems to be the best strategy for rapid detection of PZA-resistant M. tuberc ulosis.