Diversity and novel mutations in membrane transporters of Mycobacterium tuberculosis.

Autor: Khan MT; Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Pakistan., Khan TA; Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Phase V, Hayatabad, Peshawar, Khyber Pakhtunkhwa, 26000, Pakistan., Ahmad I; Department of Molecular Biology and Genetics. Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Muhammad S; Department of Chemistry, College of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia., Wei DQ; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nanshan District, Shenzhen, Guangdong, 518055, P.R. China.
Jazyk: angličtina
Zdroj: Briefings in functional genomics [Brief Funct Genomics] 2023 Apr 13; Vol. 22 (2), pp. 168-179.
DOI: 10.1093/bfgp/elac018
Abstrakt: Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), encodes a family of membrane proteins belonging to Resistance-Nodulation-Cell Division (RND) permeases also called multidrug resistance pumps. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in exporting of lipid components across the cell envelope. These proteins perform an essential role in MTB survival; however, there are no data regarding mutations in MmpL, polyketide synthase (PKS) and acyl-CoA dehydrogenase FadE proteins from Khyber Pakhtunkhwa, Pakistan. This study aimed to screen mutations in transmembrane transporter proteins including MmpL, PKS and Fad through whole-genome sequencing (WGS) in local isolates of Khyber Pakhtunkhwa province, Pakistan. Fourteen samples were collected from TB patients and drug susceptibility testing was performed. However, only three samples were completely sequenced. Moreover, 209 whole-genome sequences of the same geography were also retrieved from NCBI GenBank to analyze the diversity of mutations in MmpL, PKS and Fad proteins. Among the 212 WGS (Accession ID: PRJNA629298, PRJNA629388, and ERR2510337-ERR2510345, ERR2510546-ERR2510645), numerous mutations in Fad (n = 756), PKS (n = 479), and MmpL (n = 306) have been detected. Some novel mutations were also detected in MmpL, PKS and acyl-CoA dehydrogenase Fad. Novel mutations including Asn576Ser in MmpL8, Val943Gly in MmpL9 and Asn145Asp have been detected in MmpL3. The presence of a large number of mutations in the MTB membrane may have functional consequences on proteins. However, further experimental studies are needed to elucidate the variants' effect on MmpL, PKS and FadE functions.
(© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje