scholarly journals Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82551 ◽  
Author(s):  
Matthias Merker ◽  
Thomas A. Kohl ◽  
Andreas Roetzer ◽  
Leona Truebe ◽  
Elvira Richter ◽  
...  
2020 ◽  
Vol 69 (7) ◽  
pp. 1013-1019
Author(s):  
Tryna Tania ◽  
Pratiwi Sudarmono ◽  
R. Lia Kusumawati ◽  
Andriansjah Rukmana ◽  
Wahyu Agung Pratama ◽  
...  

Introduction. Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem globally, including in Indonesia. Whole-genome sequencing (WGS) analysis has rarely been used for the study of TB and MDR-TB in Indonesia. Aim. We evaluated the use of WGS for drug-susceptibility testing (DST) and to investigate the population structure of drug-resistant Mycobacterium tuberculosis in Java, Indonesia. Methodology. Thirty suspected MDR-TB isolates were subjected to MGIT 960 system (MGIT)-based DST and to WGS. Phylogenetic analysis was done using the WGS data. Results obtained using MGIT-based DST and WGS-based DST were compared. Results. Agreement between WGS and MGIT was 93.33 % for rifampicin, 83.33 % for isoniazid and 76.67 % for streptomycin but only 63.33 % for ethambutol. Moderate WGS–MGIT agreement was found for second-line drugs including amikacin, kanamycin and fluoroquinolone (73.33–76.67 %). MDR-TB was more common in isolates of the East Asian Lineage (63.3%). No evidence of clonal transmission of DR-TB was found among members of the tested population. Conclusion. Our study demonstrated the applicability of WGS for DST and molecular epidemiology of DR-TB in Java, Indonesia. We found no transmission of DR-TB in Indonesia.


Tuberculosis ◽  
2019 ◽  
Vol 115 ◽  
pp. 81-88 ◽  
Author(s):  
Rita Macedo ◽  
Miguel Pinto ◽  
Vítor Borges ◽  
Alexandra Nunes ◽  
Olena Oliveira ◽  
...  

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 669
Author(s):  
Igor Mokrousov ◽  
Anna Vyazovaya ◽  
Gulnora Akhmedova ◽  
Natalia Solovieva ◽  
Eugeni Turkin ◽  
...  

Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.


2016 ◽  
Vol 6 ◽  
pp. 113-117 ◽  
Author(s):  
Htin Lin Aung ◽  
Thanda Tun ◽  
Danesh Moradigaravand ◽  
Claudio U. Köser ◽  
Wint Wint Nyunt ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Joseph Yamweka Chizimu ◽  
Eddie Samuneti Solo ◽  
Precious Bwalya ◽  
Wimonrat Tanomsridachchai ◽  
Herman Chambaro ◽  
...  

Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.


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