Novel pncA mutations in pyrazinamide-resistant isolates of Mycobacterium tuberculosis

The gene coding for pyrazinamidase (PZase) activity, pncA, in Mycobacterium tuberculosis was recently cloned, and several mutations which correlate wi th in vitro resistance to pyrazinamide (PZA) have been identified. During t he development of a clinical molecular assay for the detection of PZA resis tance, two previously unreported mutations in isolates of PZA-resistant M. tuberculosis were identified. The assay that uses automated DNA sequencing is relatively rapid and allows the detection of any mutations present in th e coding region of the pncA gene. The new mutations are both point mutation s resulting in amino acid substitutions; 241T-->G results in F80V, and 511G -->C results in A171P. The identification of these mutations accentuates th e utility of automated DNA sequencing in the clinical laboratory.