Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis

• DOI: 10.1128/aac.41.3.540
• Publication Date: 2018-10-09T00:28:15Z
• Authors: A Scorpio; P Lindholm-Levy; L Heifets; R Gilman; S Siddiqi; M Cynamon; Y Zhang
• Keywords: Pyrazinamide; Single-strand conformation polymorphism

Pyrazinamide (PZA) is a first-line drug for short-course tuberculosis therapy. Resistance to PZA usually accompanied by loss of pyrazinamidase (PZase) activity in Mycobacterium tuberculosis. PZase converts bactericidal pyrazinoic acid, and the associated with resistance. The gene (pncA) encoding M. has recently been sequenced, mutations pncA were previously found small number PZA-resistant strains. To further understand genetic basis resistance determine frequency strains having mutations, we analyzed panel clinical isolates mutants made vitro. Thirty-three 38 had mutations. Among five that did not contain four be falsely resistant one was borderline PZA. 33 8 vitro contained various including nucleotide substitutions, insertions, or deletions gene. identified dispersed along gene, but some degree clustering at following regions: Gly132-Thr142, Pro69-Leu85, Ile5-Asp12. PCR-single-strand conformation polymorphism (SSCP) analysis shown useful rapid detection We conclude mutation major mechanism direct sequencing PCR SSCP should help rapidly identify