Faculty Opinions recommendation of Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes.

In the antibiotic era, Tuberculosis (TB) drugs resistance especially Rifampicin (RIF) is highly reported around the world. Resistance of RIF is caused by the mutation of genes that associated with RIF receptor. The aims of this study are detecting the Single Nucleotide Polymorphism of Rifampicin resistant genes using Whole Genome Sequencing (WGS) and analysing the profile of protein changing caused by SNP. Twenty Mycobacterium tuberculosis culture samples were passed on WGS procedure and 19 samples were adequate to further bioinformatics analysis. Single Nucleotide Polymorphisms Analysis was done using TBprofiler. Based on TBProfiler, seventeen samples were resistant to rifampicin. The mutations that cause the resistance are S450L, D435Y, H445Y, 430P, Q432K. Other Single Nucleotide Polymorphisms H835R, V534M and R224C were also found. The H835R mutants are present together with the S450L, V534M with S450L mutants, and R224C with Q432K mutants. Native protein for RNA Polymerase Subunit β used was the result of separation from the crystal structure of Mycobacterium tuberculosis H37Rv RNA polymerase (PDB: 5UHB). Binding affinity RIF to RNA Polymerase Subunit β calculated using AutoDock vina. Construction of mutant 3D structures using FoldX5. From the analysis, it was found that seventeen samples were resistant to rifampicin and two samples did not contain SNP which could cause resistance to rifampicin.

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Enriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains

Infection and Drug Resistance ◽

10.2147/idr.s152082 ◽

2018 ◽

Vol Volume 11 ◽

pp. 169-175 ◽

Cited By ~ 1

Author(s):

Mallika Lavania ◽

Itu Singh ◽

Ravindra P Turankar ◽

Anuj Gupta ◽

Madhvi Ahuja ◽

...

Keyword(s):

Rna Polymerase ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Mycobacterium Leprae ◽

Whole Genome ◽

Polymerase Gene ◽

Compensatory Mutations ◽

Rna Polymerase Gene

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Clinical and public health utility of Mycobacterium tuberculosis whole genome sequencing

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.02.114 ◽

2021 ◽

Author(s):

Alice Kizny Gordon ◽

Ben Marais ◽

Timothy M. Walker ◽

Vitali Sintchenko

Keyword(s):

Public Health ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Health Utility ◽

Whole Genome

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Whole genome sequencing data of 1110 Mycobacterium tuberculosis isolates identifies insertions and deletions associated with drug resistance

BMC Genomics ◽

10.1186/s12864-018-4734-6 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Xi Zeng ◽

Jamie Sui-Lam Kwok ◽

Kevin Yi Yang ◽

Kenneth Siu-Sing Leung ◽

Mai Shi ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Insertions And Deletions

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Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

Journal of Clinical Microbiology ◽

10.1128/jcm.00298-17 ◽

2017 ◽

Vol 55 (6) ◽

pp. 1871-1882 ◽

Cited By ~ 46

Author(s):

Joseph Shea ◽

Tanya A. Halse ◽

Pascal Lapierre ◽

Matthew Shudt ◽

Donna Kohlerschmidt ◽

...

Keyword(s):

New York ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Predictive Value ◽

New York State ◽

Whole Genome ◽

Content Type ◽

York State

ABSTRACTWhole-genome sequencing (WGS) is a newer alternative for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles while performing species identification and capturing the data necessary for genotyping. Our laboratory developed and validated a comprehensive and sensitive WGS assay to characterizeMycobacterium tuberculosisand otherM. tuberculosiscomplex (MTBC) strains, composed of a novel DNA extraction, optimized library preparation, paired-end WGS, and an in-house-developed bioinformatics pipeline. This new assay was assessed using 608 MTBC isolates, with 146 isolates during the validation portion of this study and 462 samples received prospectively. In February 2016, this assay was implemented to test all clinical cases of MTBC in New York State, including isolates and early positive Bactec mycobacterial growth indicator tube (MGIT) 960 cultures from primary specimens. Since the inception of the assay, we have assessed the accuracy of identification of MTBC strains to the species level, concordance with culture-based drug susceptibility testing (DST), and turnaround time. Species identification by WGS was determined to be 99% accurate. Concordance between drug resistance profiles generated by WGS and culture-based DST methods was 96% for eight drugs, with an average resistance-predictive value of 93% and susceptible-predictive value of 96%. This single comprehensive WGS assay has replaced seven molecular assays and has resulted in resistance profiles being reported to physicians an average of 9 days sooner than with culture-based DST for first-line drugs and 32 days sooner for second-line drugs.

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Genome Sequencing of Polydrug-, Multidrug-, and Extensively Drug-Resistant Mycobacterium tuberculosis Strains from South India

Microbiology Resource Announcements ◽

10.1128/mra.01388-18 ◽

2019 ◽

Vol 8 (12) ◽

Author(s):

Sivakumar Shanmugam ◽

Narender Kumar ◽

Dina Nair ◽

Mohan Natrajan ◽

Srikanth Prasad Tripathy ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

South India ◽

Sequence Data ◽

Whole Genome ◽

Drug Resistant ◽

Resistance Mutations ◽

Content Type ◽

Extensively Drug Resistant

The genomes of 16 clinical Mycobacterium tuberculosis isolates were subjected to whole-genome sequencing to identify mutations related to resistance to one or more anti-Mycobacterium drugs. The sequence data will help in understanding the genomic characteristics of M. tuberculosis isolates and their resistance mutations prevalent in South India.

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