Molecular characterization of PZA-resistant strains - Video abstract [ID 230774] скачать в хорошем качестве

Molecular characterization of PZA-resistant strains - Video abstract [ID 230774]

Video abstract of an original research "Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates in Southern China” published in the open access journal Infection and Drug Resistance by HM Adnan Hameed, Yaoju Tan, Md Mahmudul Islam et al. Objective: Pyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA+ upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis. Methods: Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates. Results: Our data showed that among 448M. tuberculosis clinical isolates, 113 wereMDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drugresistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZAR isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncARv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZAR. Compared with phenotypic data, 84.38%(227/269) PZAR strains with mutations in pncA+ upstream region exhibited 83.64%sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48%(4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74%(2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C−114del) in upstream of pncAwt nullified the effect of A−11G mutation and induced positive PZase activity, divergent from five PZase negative A−11G PZAR mutants. Twenty-six PZAR strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms. Conclusion: Our study revealed that PZAR rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA+ UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance. Read the full paper here: https://www.dovepress.com/detection-o...