Insight into the drug resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan.
Genome
PE
PPE
PZA
Resistance
Journal
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
ISSN: 1567-7257
Titre abrégé: Infect Genet Evol
Pays: Netherlands
ID NLM: 101084138
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
27
10
2020
revised:
31
03
2021
accepted:
08
04
2021
pubmed:
17
4
2021
medline:
13
1
2022
entrez:
16
4
2021
Statut:
ppublish
Résumé
Whole genome sequencing (WGS) is one of the most reliable methods for detection of drug resistance, genetic diversity in other virulence factor and also evolutionary dynamics of Mycobacterium tuberculosis complex (MTBC). First-line anti-tuberculosis drugs are the major weapons against Mycobacterium tuberculosis (MTB). However, the emergence of drug resistance remained a major obstacle towards global tuberculosis (TB) control program 2030, especially in high burden countries including Pakistan. To overcome the resistance and design potent drugs, genomic variations in drugs targets as well as in the virulence and evolutionary factors might be useful for better understanding and designing potential inhibitors. Here we aimed to find genomic variations in the first-line drugs targets, along with other virulence and evolutionary factors among the circulating isolates in Khyber Pakhtunkhwa, Pakistan. Samples were collected and drug susceptibility testing (DST) was performed as per WHO standard. The resistance samples were subjected to WGS. Among the five whole genome sequences, three samples (NCBI BioProject Accession: PRJNA629298, PRJNA629388) harbored 1997, 1162, and 2053 mutations. Some novel mutations have been detected in drugs targets. Similarly, numerous novel variants have also been detected in virulency and evolutionary factors, PE, PPE, and secretory system of MTB isolates. Exploring the genomic variations among the circulating isolates in geographical specific locations might be useful for future drug designing. To the best of our knowledge, this is the first study that provides useful data regarding the insight genomic variations in virulency, evolutionary factors including ESX and PE/PPE as well as drug targets, for better understanding and management of TB in a WHO declared high burden country.
Identifiants
pubmed: 33862292
pii: S1567-1348(21)00158-1
doi: 10.1016/j.meegid.2021.104861
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104861Informations de copyright
Copyright © 2021. Published by Elsevier B.V.