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

作者：Akhmetova A; Kozhamkulov U; Bismilda V; Chingissova L; Abildaev T; Dymova M^*; Filipenko M; Ramanculov E

来源：International Journal of Tuberculosis and Lung Disease, 2015, 19(2): 179-184.

DOI：10.5588/ijtld.14.0305

• pyrazinamide
• PZA
• resistance
• Mycobacterium tuberculosis
• sequencing

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.

• 出版日期2015-2