scholarly journals Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nguyen Thi Le Hang ◽  
Minako Hijikata ◽  
Shinji Maeda ◽  
Pham Huu Thuong ◽  
Jun Ohashi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bacterial Genome ◽  
Resistance Mutation ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Genome Wide ◽  
Resistant Strains

Abstract Drug-resistant tuberculosis (TB) is a serious global problem, and pathogen factors involved in the transmission of isoniazid (INH)-resistant TB have not been fully investigated. We performed whole genome sequencing of 332 clinical Mycobacterium tuberculosis (Mtb) isolates collected from patients newly diagnosed with smear-positive pulmonary TB in Hanoi, Vietnam. Using a bacterial genome-wide approach based on linear mixed models, we investigated the associations between 31-bp k-mers and clustered strains harboring katG-S315T, a major INH-resistance mutation in the present cohort and in the second panel previously published in South Africa. Five statistically significant genes, namely, PPE18/19, gid, emrB, Rv1588c, and pncA, were shared by the two panels. We further identified variants of the genes responsible for these k-mers, which are relevant to the spread of INH-resistant strains. Phylogenetic convergence test showed that variants relevant to PPE46/47-like chimeric genes were significantly associated with the same phenotype in Hanoi. The associations were further confirmed after adjustment for the confounders. These findings suggest that genomic variations of the pathogen facilitate the expansion of INH-resistance TB, at least in part, and our study provides a new insight into the mechanisms by which drug-resistant Mtb maintains fitness and spreads in Asia and Africa.

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

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.

scholarly journals 799. Genetic Diversity of Mycobacterium tuberculosis Strains Causing Drug-Resistant Tuberculosis in Central Region of Mozambique: The Whole-Genome Sequencing

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S286-S287
Author(s):  
Evangelina Namburete
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Central Region ◽  
Disease Spread ◽  
Whole Genome ◽  
Drug Resistant ◽  
Illumina Hiseq ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

Abstract Background Knowing the genetic diversity of M. tuberculosis strains causing drug-resistant tuberculosis (DR-TB) in high burden TB and low resources countries such as Mozambique is a key factor to TB disease spread control and world TB epidemic control. Whole-genome sequencing (WGS) better describes molecular diversity, lineages and sub lineages, relationship between strains, underline mutations conferring drug-resistant TB, which may not be shown by molecular and phenotypic tests. As far as we know this is the first study that describes genetic diversity of M. tuberculosis strains causing DR-TB and using WGS in central region of Mozambique.We aim to describe genetic diversity of M. tuberculosis strains causing DR-TB in central Mozambique. Methods A total of 35 strains from Beira Mozambique were evaluated with genotypic tests (Genotype MTBDRplus™, and MTBDRsl™); phenotypic (MGIT-SIRE™) and DST. All isolates resistant to isoniazid (H) or rifampicin (R) or both were submitted to WGS Illumina HiSeq 2000 and analyzed with TB profiler database and phylogenetic tree was done using Figtree tool. This was a descriptive cross-sectional study. Results WGS shown that strains analyzed, belongs to three of six major lineages, with Lineage 4: 25(71.4%); Lineage 1: 5(14.3%); and Lineage 2 Beijing family: 5(14.3%)]. All pre-XDR strains 3(8.6%) were from lineage 4.3. By WGS, all 35 strains had any mutations conferring DR-TB while in one strain, mutation was not shown by genotypic neither phenotypic DST. Compared with genotypic tests, WGS had best performance in showing mutation conferring resistance to etambutol 12/35 (34.3%) and 7/35 (20%). Conclusion The DR-TB disease in Beira Mozambique is mainly caused by M. tuberculosis strains of Lineage 4, sub-lineage 3 although lineage 1 and 2 are also present. WGS shows underline mutations causing DR–TB that are not detected by genotypic and phenotypic DST test. Disclosures All authors: No reported disclosures.

scholarly journals Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

2019 ◽  
Vol 25 (3) ◽  
pp. 538-546
Author(s):  
Imen Bouzouita ◽  
Andrea Maurizio Cabibbe ◽  
Alberto Trovato ◽  
Henda Daroui ◽  
Asma Ghariani ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant

scholarly journals A67 Use of next-generation whole-genome sequencing to understand drug-resistant Mycobacterium tuberculosis in Botswana

2018 ◽  
Vol 4 (suppl_1) ◽  
Author(s):  
T Iketleng ◽  
T Mogashoa ◽  
B Mbeha ◽  
L Letsibogo ◽  
J Makhema ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Next Generation

scholarly journals Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117771 ◽  
Author(s):  
Asho Ali ◽  
Zahra Hasan ◽  
Ruth McNerney ◽  
Kim Mallard ◽  
Grant Hill-Cawthorne ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Lesion Heterogeneity and Long-Term Heteroresistance in Multidrug-Resistant Tuberculosis

2021 ◽  
Author(s):  
Yiwang Chen ◽  
Lecai Ji ◽  
Qingyun Liu ◽  
Jinli Li ◽  
Chuangyue Hong ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Drug Resistant ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

Abstract Tuberculosis heteroresistance, in which only a fraction of the bacteria in a patient with tuberculosis contains drug-resistant mutations, has been a rising concern. However, its origins and prevalence remain elusive. Here, whole-genome sequencing was performed on 83 serial isolates from 31 patients with multidrug-resistant tuberculosis, and heteroresistance was detected in isolates from 21 patients (67.74%). Heteroresistance persisted in the host for long periods, spanning months to years, and was associated with having multiple tubercular lesions. Our findings indicate that heteroresistance is common and persistent in patients with multidrug-resistant tuberculosis and may affect the success of their treatment regimens.

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