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 language | English |
|---|---|
| Pages (from-to) | 179-184 |
| Number of pages | 6 |
| Journal | International Journal of Tuberculosis and Lung Disease |
| Volume | 19 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2015 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Mutations in the pncAand rpsAgenes among 77 Mycobacterium tuberculosis isolates in Kazakhstan
AU - Akhmetova, A.
AU - Kozhamkulov, U.
AU - Bismilda, V.
AU - Chingissova, L.
AU - Abildaev, T.
AU - Dymova, M.
AU - Filipenko, M.
AU - Ramanculov, E.
PY - 2015/2/1
Y1 - 2015/2/1
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.
KW - Mycobacterium tuberculosis
KW - Pyrazinamide
KW - PZA
KW - Resistance
KW - Sequencing
UR - http://www.scopus.com/inward/record.url?scp=84937147628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937147628&partnerID=8YFLogxK
U2 - 10.5588/ijtld.14.0305
DO - 10.5588/ijtld.14.0305
M3 - Article
VL - 19
SP - 179
EP - 184
JO - International Journal of Tuberculosis and Lung Disease
JF - International Journal of Tuberculosis and Lung Disease
SN - 1027-3719
IS - 2
ER -