In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment

BMC Genomics
Yuhui XuZhaogang Sun

Abstract

In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations. All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates. Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumu...Continue Reading

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Citations

Jun 21, 2019·Current Pharmaceutical Design·Prasad MinakshiGaya Prasad
Nov 20, 2020·Journal of Drug Targeting·Xiaohong XiangJianping Xie
Oct 30, 2020·Molecular Biology and Evolution·Yair E Gatt, Hanah Margalit
Jan 16, 2021·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·Andrea SanchiniStefan Kröger
Nov 23, 2020·The Journal of Antimicrobial Chemotherapy·Gerrit BrandisDiarmaid Hughes
Apr 26, 2021·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Yi HuBiao Xu
May 18, 2021·Synthetic and Systems Biotechnology·Fei LiuPengcheng Fu

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Datasets Mentioned

BETA
AL123456

Methods Mentioned

BETA
PCR

Software Mentioned

Population Analysis with Reticulate Trees ( PopArt
LengthSort Perl scripts
SOAPsnp
DynamicTrim
SOAP2
SMRT Portal
GapCloser
SolexaQA
kSNP3
SOAPdenovo

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