Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms

Srinand Sreevatsan, Xi Pan, Ying Zhang, Barry N. Kreiswirth, James M. Musser

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

A gene (pncA) with mutations associated with pyrazinamide resistance in Mycobacterium tuberculosis complex members was characterized in 67 pyrazinamide-resistant and 51 pyrazinamide-susceptible isolates recovered 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 pyrazinamidase. A total of 17 previously undescribed mutations were found, including upstream mutations, missense changes, nucleotide insertions and deletions, and termination mutations. The mutations were arrayed along virtually the entire length of the gene. These data are further evidence that most drug resistance in M. tuberculosis is due to simple mutations occurring in chromosomally encoded genes rather than to acquisition of resistance genes by horizontal transfer events.

Original languageEnglish (US)
Pages (from-to)636-640
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume41
Issue number3
DOIs
StatePublished - Mar 1997

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