Determination of drug resistance of the clinical strains of Mycobacterium tuberculosis to pyrazinamide

Abstract

A description is given of the pyrazinamide-resistant clinical strains of M. tuberculosis derived from the sputum of patients treated in tuberculosis clinics in Tula (June 2001–July 2002). It was demonstrated that 30.3% (n = 91) of strains were resistant to pyrazinamide. It was learned that these strains were resistant to other antituberculosis drugs in most cases. The method of PCR sequencing was used to find mutations in the pncA gene, which determines the resistance to pyrazinamide. 44 different types of mutations localized in 28 codons were detected. The predominance of mutations in codons 57 (13.2%), 63 (7.7%), 97 (7.7%), 12 (6.6%), and 103 (6.6%) and in the −11 (6.6%) promoter of pncA was observed in the pyrazinamide-resistant strains. Several new mutations that determine the resistance of clinical strains of M. tuberculosis to pyrazinamide were described. A strong correlation between the resistance of mycobacteria to pyrazinamide and activity of pyrazinamidase was observed.