scholarly journals Whole Genome Sequencing of Drug Resistant and Drug Susceptible Mycobacterium tuberculosis Isolates From Tigray Region, Ethiopia

2021 ◽  
Vol 12 ◽  
Author(s):  
Letemichael Negash Welekidan ◽  
Solomon Abebe Yimer ◽  
Eystein Skjerve ◽  
Tsehaye Asmelash Dejene ◽  
Håvard Homberset ◽  
...  

Background: Tuberculosis, mainly caused by Mycobacterium tuberculosis (Mtb), is an ancient human disease that gravely affects millions of people annually. We wanted to explore the genetic diversity and lineage-specific association of Mtb with drug resistance among pulmonary tuberculosis patients.Methods: Sputum samples were collected from pulmonary tuberculosis patients at six different healthcare institutions in Tigray, Ethiopia, between July 2018 and August 2019. DNA was extracted from 74 Mtb complex isolates for whole-genome sequencing (WGS). All genomes were typed and screened for mutations with known associations with antimicrobial resistance using in silico methods, and results were cross-verified with wet lab methods.Results: Lineage (L) 4 (55.8%) was predominant, followed by L3 (41.2%); L1 (1.5%) and L2 (1.5%) occurred rarely. The most frequently detected sublineage was CAS (38.2%), followed by Ural (29.4%), and Haarlem (11.8%). The recent transmission index (RTI) was relatively low. L4 and Ural strains were more resistant than the other strains to any anti-TB drug (P < 0.05). The most frequent mutations to RIF, INH, EMB, SM, PZA, ETH, FLQs, and 2nd-line injectable drugs occurred at rpoB S450L, katG S315T, embB M306I/V, rpsL K43R, pncA V139A, ethA M1R, gyrA D94G, and rrs A1401G, respectively. Disputed rpoB mutations were also shown in four (16%) of RIF-resistant isolates.Conclusion: Our WGS analysis revealed the presence of diverse Mtb genotypes. The presence of a significant proportion of disputed rpoB mutations highlighted the need to establish a WGS facility at the regional level to monitor drug-resistant mutations. This will help control the transmission of DR-TB and ultimately contribute to the attainment of 100% DST coverage for TB patients as per the End TB strategy.

2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Sivakumar Shanmugam ◽  
Narender Kumar ◽  
Dina Nair ◽  
Mohan Natrajan ◽  
Srikanth Prasad Tripathy ◽  
...  

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.


2019 ◽  
Vol 25 (3) ◽  
pp. 538-546
Author(s):  
Imen Bouzouita ◽  
Andrea Maurizio Cabibbe ◽  
Alberto Trovato ◽  
Henda Daroui ◽  
Asma Ghariani ◽  
...  

2018 ◽  
Vol 4 (suppl_1) ◽  
Author(s):  
T Iketleng ◽  
T Mogashoa ◽  
B Mbeha ◽  
L Letsibogo ◽  
J Makhema ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117771 ◽  
Author(s):  
Asho Ali ◽  
Zahra Hasan ◽  
Ruth McNerney ◽  
Kim Mallard ◽  
Grant Hill-Cawthorne ◽  
...  

Author(s):  
Zainal Arifin Mustapha ◽  
Jaeyres Jani ◽  
Cheronie Shely Stanis ◽  
Dg Syahidah Nadiah Abdull Majid ◽  
Chin Kai Ling ◽  
...  

This paper reports on the whole-genome sequencing of a streptomycin-resistant Mycobacterium tuberculosis strain that was isolated from a patient with pulmonary tuberculosis in Sabah state of Malaysian Borneo. The strain belongs to the EAI2-Manila family of lineage 1 and is clustered with M. tuberculosis strains from the Philippines, India, and Taiwan.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160992 ◽  
Author(s):  
Kiatichai Faksri ◽  
Jun Hao Tan ◽  
Areeya Disratthakit ◽  
Eryu Xia ◽  
Therdsak Prammananan ◽  
...  

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Farzam Vaziri ◽  
Thomas A. Kohl ◽  
Hasan Ghajavand ◽  
Mansour Kargarpour Kamakoli ◽  
Matthias Merker ◽  
...  

ABSTRACT The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains is a critical global health problem. Between 2014 and 2018, 606 MTBC strains were isolated from 13,892 suspected pulmonary tuberculosis (TB) patients in Tehran, Iran, including 16 (2.6%) MDR-TB cases. A combination of phenotypic and genotypic methods (whole-genome sequencing) was employed for the identification of additional drug resistances and strain-to-strain genetic distances as a marker for recent transmission events. MDR and extensively drug-resistant (XDR) TB cases were almost exclusively infected by lineage 2/Beijing strains (14/16, P < 0.001). We further showed that recent transmission and/or recent introduction of lineage 2/Beijing strains contribute to high XDR-TB rates among all MDR-TB cases and should be considered an emerging threat for TB control in Tehran. In addition, the extensive pre-existing drug resistance profiles of MDR/XDR strains will further challenge TB diagnostics in the region.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nguyen Thi Le Hang ◽  
Minako Hijikata ◽  
Shinji Maeda ◽  
Pham Huu Thuong ◽  
Jun Ohashi ◽  
...  

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.


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