ArticleBMC infectious diseases2019
Pyrazinamide resistance and mutations in pncA among isolates of Mycobacterium tuberculosis from Khyber Pakhtunkhwa, Pakistan.
Article in BMC infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- The epidemiology and gene mutation characteristics of pyrazinamide-resistantEmerging microbes & infections · 2025Article
- Characterization of Drug Resistance Mutations inMicroorganisms · 2025Article
- Whole-genome sequencing analysis to identify antimicrobial resistance regions and virulence factors in Mycobacterium tuberculosis isolates from the Amhara Region, Ethiopia.Scientific reports · 2025Article
- Enhancing diagnostic efficiency of pyrazinamide resistance inCurrent research in microbial sciences · 2025Article
- A robust computational quest: Discovering potential hits to improve the treatment of pyrazinamide-resistant Mycobacterium tuberculosis.Journal of cellular and molecular medicine · 2024Article
- OvercomingACS omega · 2023Review
- Anti-tuberculosis drug resistance in Slovakia, 2018-2019: The first whole-genome epidemiological study.Journal of clinical tuberculosis and other mycobacterial diseases · 2022Review
- Characterization of Fluoroquinolone-Resistant and Multidrug-ResistantInfection and drug resistance · 2022Article
- Wastewater-Based Surveillance of Antibiotic Resistance Genes Associated with Tuberculosis Treatment Regimen in KwaZulu Natal, South Africa.Antibiotics (Basel, Switzerland) · 2021Article
- Genome analyses of 174 strains ofMicrobial genomics · 2021Article
- A computational perspective on the dynamic behaviour of recurrent drug resistance mutations in the pncA gene fromRSC advances · 2021Article
- Insights Into Mutations Induced Conformational Changes and Rearrangement of FeFrontiers in molecular biosciences · 2021Article
- Structural and Genomic Insights Into Pyrazinamide Resistance inFrontiers in molecular biosciences · 2021Article
- Application of Computational Methods in Understanding Mutations inFrontiers in molecular biosciences · 2021Review
- Mechanistic analysis of A46V, H57Y, and D129N in pyrazinamidase associated with pyrazinamide resistance.Saudi journal of biological sciences · 2020Article
- Pyrazinamide resistance of novel mutations inRSC advances · 2020Article
- Treatment outcomes of patients with tuberculosis in war affected region of Khyber Pakhtunkhwa, Pakistan.BMC infectious diseases · 2020Article
- Rapid Pyrazinamide Drug Susceptibility Testing using a Closed-Tube PCR Assay of the Entire pncA gene.Scientific reports · 2020Article
- Article
- Pyrazinamide Resistance and Mutation Patterns Among Multidrug-ResistantInfection and drug resistance · 2020Article
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7 authors.
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Abstract
backgroundPyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance. The aim of the present study was to explore the molecular characterization of PZA resistance in a Pashtun-dominated region of Khyber Pakhtunkhwa, Pakistan.
methodsWe performed drug susceptibility testing (DST) on 753 culture-positive isolates collected from the Provincial Tuberculosis Control Program Khyber Pakhtunkhwa using the BACTEC MGIT 960 PZA method. In addition, the pncA gene was sequenced in PZA-resistant isolates, and PZA susceptibility testing results were used to determine the sensitivity and specificity of pncA gene mutations.
resultsA total of 69 isolates were PZA resistant (14.8%). Mutations were investigated in 69 resistant, 26 susceptible and one H37Rv isolates by sequencing. Thirty-six different mutations were identified in PZA-resistant isolates, with fifteen mutations, including 194_203delCCTCGTCGTG and 317_318delTC, that have not been reported in TBDRM and GMTV Databases and previous studies. Mutations Lys96Thr and Ser179Gly were found in the maximum number of isolates (n = 4 each). We did not detect mutations in sensitive isolates, except for the synonymous mutation 195C > T (Ser65Ser). The sensitivity and specificity of the pncA sequencing method were 79.31% (95% CI, 69.29 to 87.25%) and 86.67% (95% CI, 69.28 to 96.24%).
conclusionMutations in the pncA gene in circulating isolates of geographically distinct regions, especially in high-burden countries, should be investigated for better control and management of drug-resistant TB. Molecular methods for the investigation of PZA resistance are better than DST.
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