Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan

• Published in: The international journal of tuberculosis and lung disease 2015-02, Vol.19 (2), p.179-184
• Main Authors: Akhmetova, A., Kozhamkulov, U., Bismilda, V., Chingissova, L., Abildaev, T., Dymova, M., Filipenko, M., Ramanculov, E.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Amidohydrolases - genetics; Antitubercular Agents - pharmacology; Child; DNA, Bacterial - genetics; Drug Resistance, Bacterial - genetics; Female; Genotype; Humans; Kazakhstan; Male; Microbial Sensitivity Tests; Middle Aged; Minisatellite Repeats; Mutation; Mycobacterium Tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Pyrazinamide; Pyrazinamide - pharmacology; Pza; Resistance; Ribosomal Proteins - genetics; Sequence Analysis, DNA - methods; Sequencing; Tuberculosis - drug therapy; Tuberculosis - microbiology; Young Adult
• ISSN: 1027-3719; 1815-7920
• DOI: 10.5588/ijtld.14.0305

SETTING: Pyrazinamide (PZA), an important first-line drug for anti-tuberculosis treatment, demonstrates potent activity against semi-dormant bacilli in acidic environments. However, the diagnosis of PZA resistance is often impeded by technical difficulties.OBJECTIVE: To characterise mutations in the pncA and rpsA genes among PZA-resistant and PZA-susceptible clinical Mycobacterium tuberculosis isolates circulating in Kazakhstan. The potential use of genotyping to identify PZA resistance was also investigated.DESIGN: PZA drug susceptibility testing and pncA and rpsA gene sequencing were performed on 77 clinical M. tuberculosis isolates; mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was performed on 74 clinical M. tuberculosis isolates.RESULTS: Of the 77 clinical M. tuberculosis isolates, 41 (53.2%) were phenotypically resistant to PZA, whereas 36 (46.7%) were susceptible; 48 (62.3%) of these isolates were also multidrug-resistant (MDR). Furthermore, 38 (49.3%) clinical isolates showed mutations in the pncA gene and its flanking region; the majority of these isolates (n = 36, 94.7%) were also MDR. Gene sequencing showed that only synonymous substitutions affecting rpsA occurred. MIRU-VNTR typing revealed that 78.4% of isolates were of the Beijing genotype.CONCLUSIONS: Sequencing revealed that mutations in pncA, but not in rpsA, occurred in PZA-resistant M. tuberculosis isolates circulating in the territory of Kazakhstan.