scholarly journals Whole-genome sequencing analysis of multidrug-resistant Mycobacterium tuberculosis from Java, Indonesia

2020 ◽  
Vol 69 (7) ◽  
pp. 1013-1019
Author(s):  
Tryna Tania ◽  
Pratiwi Sudarmono ◽  
R. Lia Kusumawati ◽  
Andriansjah Rukmana ◽  
Wahyu Agung Pratama ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Major Public Health Problem ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Mdr Tb

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.

scholarly journals Whole genome sequencing of M.tuberculosis in Kazakhstan: preliminary data

2014 ◽  
Vol 2 ◽  
Author(s):  
Ulykbek Kairov ◽  
Ulan Kozhamkulov ◽  
Saule Rakhimova ◽  
Ayken Askapuli ◽  
Maxat Zhabagin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Preliminary Data ◽  
Sequence Data ◽  
Public Health Problem ◽  
Read Length ◽  
Major Public Health Problem ◽  
Whole Genome ◽  
Average Read Length

Background: Tuberculosis is a major public health problem which infects one third of the world’s population, resulting in more than two million deaths every year. The emergence of whole genome sequencing (WGS) technologies as a primary research tool has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (MTB) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission, and treatment. To our knowledge, studies involving WGS of Kazakhstani strains of M. tuberculosis have not yet been performed.Aim: To perform whole genome sequencing of M. tuberculosis strains isolated in Kazakhstan and analyze sequence data (first experience and preliminary data).Results: In the present report, we announce the whole-genome sequences of the two clinical isolates of Mycobacterium tuberculosis, MTB-489 and MTB-476, isolated from the Almaty region. These strains were part of a repository that was created during our project “Creating prerequisites of personalized approach in the diagnosis and treatment of tuberculosis, based on whole genome-sequencing of M. tuberculosis”. Two strains were isolated from sputum samples of patients P1 and P2. Phenotypically, two isolates were drug-susceptible M. tuberculosis. Sequence data was compared with the publicly available data on M. tuberculosis laboratory strain H37Rv and others. The sequencing of the strains was performed on a Roche 454 GS FLX+ next-generation sequencing platform using a standard protocol for a shotgun genome library. The whole genome sequencing was performed for two M.tuberculosis isolates MTB-476 and MTB-489. 96 M bp with an average read length of 520 bp, approximately 21.8X coverage and 104.2 M bp with an average read length of 589 bp and approximately 23.7X coverage were generated for the MTB-476 and MTB-489, respectively. The genome of MTB-476 consists of 257 contigs, 4204 CDS, 46 tRNAs and 3 rRNAs. MTB-489 has 187 contigs, 4183 CDS, 45 tRNAs and 3rRNAs.Conclusion: The results of genome assembling have been submitted into NCBI GenBank and are available for public access under the accession numbers AZBA00000000 and AZAZ00000000. These genome assemblies can be useful for comparative genome analysis and for identification of novel SNPs and gene variants in genomes of M.tuberculosis.

scholarly journals Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 669
Author(s):  
Igor Mokrousov ◽  
Anna Vyazovaya ◽  
Gulnora Akhmedova ◽  
Natalia Solovieva ◽  
Eugeni Turkin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genetic Variation ◽  
Whole Genome Sequencing ◽  
Treatment Regimen ◽  
Genome Sequencing ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

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.

scholarly journals Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Joseph Yamweka Chizimu ◽  
Eddie Samuneti Solo ◽  
Precious Bwalya ◽  
Wimonrat Tanomsridachchai ◽  
Herman Chambaro ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Regulatory Region ◽  
Multidrug Resistant ◽  
Epidemiological Methods ◽  
Whole Genome ◽  
Recent Transmission ◽  
Mdr Tb

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.

scholarly journals Extensive global movement of multidrug-resistant M. tuberculosis strains revealed by whole-genome analysis

Thorax ◽  
2019 ◽  
Vol 74 (9) ◽  
pp. 882-889 ◽  
Author(s):  
Keira A Cohen ◽  
Abigail L Manson ◽  
Thomas Abeel ◽  
Christopher A Desjardins ◽  
Sinead B Chapman ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Data Sharing ◽  
Genome Sequencing ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Global Spread ◽  
Mdr Tb ◽  
Global Movement ◽  
Genomic Studies

BackgroundWhile the international spread of multidrug-resistant (MDR) Mycobacterium tuberculosis strains is an acknowledged public health threat, a broad and more comprehensive examination of the global spread of MDR-tuberculosis (TB) using whole-genome sequencing has not yet been performed.MethodsIn a global dataset of 5310 M. tuberculosis whole-genome sequences isolated from five continents, we performed a phylogenetic analysis to identify and characterise clades of MDR-TB with respect to geographic dispersion.ResultsExtensive international dissemination of MDR-TB was observed, with identification of 32 migrant MDR-TB clades with descendants isolated in 17 unique countries. Relatively recent movement of strains from both Beijing and non-Beijing lineages indicated successful global spread of varied genetic backgrounds. Migrant MDR-TB clade members shared relatively recent common ancestry, with a median estimate of divergence of 13–27 years. Migrant extensively drug-resistant (XDR)-TB clades were not observed, although development of XDR-TB within migratory MDR-TB clades was common.ConclusionsApplication of genomic techniques to investigate global MDR migration patterns revealed extensive global spread of MDR clades between countries of varying TB burden. Further expansion of genomic studies to incorporate isolates from diverse global settings into a single analysis, as well as data sharing platforms that facilitate genomic data sharing across country lines, may allow for future epidemiological analyses to monitor for international transmission of MDR-TB. In addition, efforts to perform routine whole-genome sequencing on all newly identified M. tuberculosis, like in England, will serve to better our understanding of the transmission dynamics of MDR-TB globally.

scholarly journals A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt

2017 ◽  
Vol 22 (2) ◽  
Author(s):  
Lena Fiebig ◽  
Thomas A Kohl ◽  
Odette Popovici ◽  
Margarita Mühlenfeld ◽  
Alexander Indra ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Universal Access ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
The European Union ◽  
Cross Border ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.

scholarly journals Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017–2019: an ECDC pilot study

2020 ◽  
Vol 57 (1) ◽  
pp. 2002272
Author(s):  
Elisa Tagliani ◽  
Richard Anthony ◽  
Thomas A. Kohl ◽  
Albert de Neeling ◽  
Vlad Nikolayevskyy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pilot Study ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Surveillance System ◽  
European Economic Area ◽  
Whole Genome ◽  
Cross Border ◽  
Lessons Learnt ◽  
Mdr Tb

Whole genome sequencing (WGS) can be used for molecular typing and characterisation of Mycobacterium tuberculosis complex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learnt to be considered for the future development of a WGS-based surveillance system.WGS and epidemiological data of patients with rifampicin-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) were collected from EU/EEA countries between January 2017 and December 2019. WGS-based genetic relatedness analysis was performed using a standardised approach including both core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP)-based calculation of distances on all WGS data that fulfilled minimum quality criteria to ensure data comparability.A total of 2218 RR/MDR-MTBC isolates were collected from 25 countries. Among these, 56 cross-border clusters with increased likelihood of recent transmission (≤5 SNPs distance) comprising 316 RR/MDR-MTBC isolates were identified. The cross-border clusters included between two and 30 resistant isolates from two to six countries, demonstrating different RR/MDR-TB transmission patterns in Western and Eastern EU countries.This pilot study shows that a WGS-based surveillance system is not only feasible but can efficiently elucidate the dynamics of in-country and cross-border RR/MDR-TB transmission across EU/EEA countries. Lessons learnt from this study highlight that the establishment of an EU/EEA centralised WGS-based surveillance system for TB will require strengthening of national integrated systems performing prospective WGS surveillance and the development of clear procedures to facilitate international collaboration for the investigation of cross-border clusters.

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