Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance.
Dipti ShresthaBhagwan MaharjanJeewan ThapaMwangala Lonah AkapelwaPrecious BwalyaJoseph Yamweka ChizimuChie NakajimaYasuhiko SuzukiPublished in: Current issues in molecular biology (2022)
Without the proper information on pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis (MTB), PZA is inappropriately recommended for the treatment of both susceptible and multidrug-resistant tuberculosis (MDR-TB) in Nepal. This study aimed to collect information regarding PZA susceptibility in MTB isolates from Nepal by analyzing pncA and its upstream regulatory region (URR). A total of 211 MTB isolates were included in this study. Sequence analysis of pncA and its URR was performed to assess PZA resistance. First-line drug susceptibility testing, spoligotyping, and sequence analysis of rpoB , katG , the inhA regulatory region, gyrA , gyrB , and rrs were performed to assess their association with pncA mutation. Sequencing results reveal that 125 (59.2%) isolates harbored alterations in pncA and its URR. A total of 57 different mutation types (46 reported and 11 novel) were scattered throughout the whole length of the pncA gene. Eighty-seven isolates (41.2%) harbored mutations in pncA , causing PZA resistance in MTB. There was a more significant association of pncA alterations in MDR/pre-extensively drug-resistant (Pre-XDR) TB than in mono-resistant/pan-susceptible TB ( p < 0.005). This first report on the increasing level of PZA resistance in DR-TB in Nepal highlights the importance of PZA susceptibility testing before DR-TB treatment.
Keyphrases
- mycobacterium tuberculosis
- multidrug resistant
- drug resistant
- pulmonary tuberculosis
- acinetobacter baumannii
- gram negative
- tertiary care
- klebsiella pneumoniae
- emergency department
- genome wide
- healthcare
- dna methylation
- single cell
- pseudomonas aeruginosa
- quantum dots
- combination therapy
- human immunodeficiency virus
- social media
- copy number
- loop mediated isothermal amplification