MUTATIONS ASSOCIATED WITH PYRAZINAMIDE RESISTANCE IN PNCA OF MYCOBACTERIUM-TUBERCULOSIS COMPLEX ORGANISMS

A gene (pncA) with mutations associated with pyrazinamide resistance i n Mycobacterium tuberculosis complex members was characterized in 67 p yrazinamide-resistant and 51 pyrazinamide-susceptible isolates recover ed from diverse geographic localities and anatomic sites and typed by IS6110 profiling, All pyrazinamide-susceptible organisms had identical pncA alleles, In striking contrast, 72% of the 67 resistant organisms had pncA mutations that altered the primary amino acid sequence of py razinamidase. A total of 17 previously undescribed mutations were foun d, including upstream mutations, missense changes, nucleotide insertio ns and deletions, and termination mutations, The mutations were arraye d along virtually the entire length of the gene, These data are furthe r evidence that most drug resistance in M. tuberculosis is due to simp le mutations occurring in chromosomally encoded genes rather than to a cquisition of resistance genes by horizontal transfer events.