Mutations in the pncAand rpsAgenes among 77 Mycobacterium tuberculosis isolates in Kazakhstan

A. Akhmetova, U. Kozhamkulov, V. Bismilda, L. Chingissova, T. Abildaev, M. Dymova, M. Filipenko, E. Ramanculov

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 (MIRUVNTR) 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.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalInternational Journal of Tuberculosis and Lung Disease
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 1 2015
Externally publishedYes

Fingerprint

Kazakhstan
Pyrazinamide
Mycobacterium tuberculosis
Mutation
Genes
Minisatellite Repeats
Pharmaceutical Preparations
Bacillus
Tuberculosis
Genotype

Keywords

  • Mycobacterium tuberculosis
  • Pyrazinamide
  • PZA
  • Resistance
  • Sequencing

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Mutations in the pncAand rpsAgenes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. / Akhmetova, A.; Kozhamkulov, U.; Bismilda, V.; Chingissova, L.; Abildaev, T.; Dymova, M.; Filipenko, M.; Ramanculov, E.

In: International Journal of Tuberculosis and Lung Disease, Vol. 19, No. 2, 01.02.2015, p. 179-184.

Research output: Contribution to journalArticle

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abstract = "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 (MIRUVNTR) 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.",
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AU - Abildaev, T.

AU - Dymova, M.

AU - Filipenko, M.

AU - Ramanculov, E.

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N2 - 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 (MIRUVNTR) 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.

AB - 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 (MIRUVNTR) 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.

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