Author response: Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area

Guerra-Assunção, JA; Crampin, AC; Houben, R M G J; Mzembe, Themba; Mallard, Kim; Coll, Francesc Español i; Khan, Palwasha; Banda, Louis; Chiwaya, Arthur; Pereira, Rpa; McNerney, Ruth; Fine, P. E. M.; Parkhill, Julian; Clark, Taane G.; Glynn, J.R.

doi:10.7554/elife.05166.015

Cited by 5 publications

(5 citation statements)

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“…bovis dataset (n = 352; Supplementary File 2) was assembled. Genomes were selected based on the following criteria: they were previously published [25,40,[47][48][49][50][51] and represented the currently understood M. bovis diversity. All previously characterized clonal complexes (Af1, Af2, Eu1, Eu2, and Eu3) and uncharacterized lineages (Unknown1 to Unknown8) from Loiseau et al [40] were included.…”

Section: Isolate Selection Culturing and Preparation Of Genomic Dnamentioning

confidence: 99%

Population structure and transmission ofMycobacterium bovisin Ethiopia

Almaw

Mekonnen

Mihret

et al. 2020

Preprint

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Bovine tuberculosis (bTB) is endemic in cattle in Ethiopia, a country that hosts the largest national cattle herd in Africa. The intensive dairy sector, most of which is peri-urban, has the highest prevalence of disease. Previous studies in Ethiopia have demonstrated that the main cause is Mycobacterium bovis (M. bovis), which has been investigated using conventional molecular tools including deletion typing, spoligotyping and Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). Here we use whole genome sequencing (WGS) to examine the population structure of M. bovis in Ethiopia. A total of 134 M. bovis isolates were sequenced including 128 genomes from 85 mainly dairy cattle and six genomes isolated from humans, originating from 12 study sites across Ethiopia. These genomes provided a good representation of the previously described population structure of M. bovis, based on spoligotyping and demonstrated that the population is dominated by the clonal complexes African 2 (Af2) and European 3 (Eu3). A range of within-host diversity was observed amongst the isolates and evidence was found for both short- and long-distance transmission. Detailed analysis of available genomes from the Eu3 clonal complex combined with previously published genomes revealed two distinct introductions of this clonal complex into Ethiopia between 1950 and 1987, likely from Europe. This work is important to help better understand bTB transmission in cattle in Ethiopia and can potentially inform national strategies for bTB control in Ethiopia and beyond.

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Section: Isolate Selection Culturing and Preparation Of Genomic Dnamentioning

confidence: 99%

Population structure and transmission ofMycobacterium bovisin Ethiopia

Almaw

Mekonnen

Mihret

et al. 2020

Preprint

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“…A high degree of clustering of drug resistant TB isolates has been observed in parts of Africa [43,44,45,46]; this is of great concern as it implies that there is recent and ongoing transmission of drug resistant TB strains within the region. Furthermore, a correlation between drug resistant strains in the adult population and in children has been demonstrated [47], suggestive of adult to child transmission.…”

Section: Population Structure Of Drug Resistant Tb Genotypes In Africamentioning

confidence: 99%

Molecular epidemiology of drug resistant Mycobacterium tuberculosis in Africa: a systematic review

Chisompola

Streicher

Muchemwa

et al. 2020

Preprint

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Background The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. MDR-TB is defined as resistance to isoniazid and rifampicin, while XDR-TB is defined as MDR-TB with added resistance to any of the second line injectable drugs and any fluoroquinolone. The highest burden of drug resistant TB is seen in countries further experiencing an HIV epidemic. The molecular mechanisms of drug resistance as well as the evolution of drug resistant TB strains have been widely studied using various genotyping tools. The study aimed to analyse the drug resistant lineages in circulation and the transmission dynamics of these lineages in Africa by describing outbreaks, nosocomial transmission and migration. Viewed as a whole, this can give a better insight into the transmission dynamics of drug resistant TB in Africa. Methods A systematic review was performed on peer reviewed original research extracted from PubMed reporting on the lineages associated with drug resistant TB from African countries, and their association with outbreaks, nosocomial transmission and migration. The search terms “Tuberculosis AND drug resistance AND Africa AND (spoligotyping OR molecular epidemiology OR IS6110 OR MIRU OR DNA fingerprinting OR RFLP OR VNTR OR WGS)” were used to identify relevant articles reporting the molecular epidemiology of drug resistant TB in Africa. Results Diverse genotypes are associated with drug resistant TB in Africa, with variations in strain predominance within the continent. Lineage 4 predominates across Africa demonstrating the ability of these “modern strains” to adapt and spread easily. Most studies under review reported primary drug resistance as the predominant type of transmission. Drug resistant TB strains are associated with community and nosocomial outbreaks involving MDR- and XDR-TB strains. The under-use of molecular epidemiological tools is of concern, resulting in gaps in knowledge of the transmission dynamics of drug resistant TB on the continent.Conclusions Genetic diversity of M. tuberculosis strains has been demonstrated across Africa implying that diverse genotypes are driving the epidemiology of drug resistant TB across the continent.

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“…On accessing the SNP distribution among strains from the same locality versus strains from different locality especially for villages with the highest representative numbers for the different lineages, a threshold of 8 SNPs was deduced to distinguish transmission links (Figure S3-6). The cut-off is similar to those used in other studies (124,128). There were 17 genomic clusters (14-Beijing lineage, three-Euro-American lineage) constituting of 74 isolates (65-Beijing lineage, nine-Euro-American lineage) (Figure 3.4…”

Section: Transmissionmentioning

confidence: 78%

“…19-1 (251). The previous studies (109,128,142,261), to the assembly and H37Rv reference genome, then used Sniffles (262) on the resultant files. The identified insertion sequences within the assembly had GC content calculated using GC calculator (Biologics International Corp, Indianapolis, USA).…”

Section: Minion ® and Illumina Data Analysismentioning

confidence: 99%

“…They characterized 390 isolates to investigate community outbreaks derived from MIRU-VNTR and were able to infer direction of transmission through setting an upper threshold of 5 SNPs, identified super-spreaders and estimated mutation rate at 0.5 SNPs/genome/year. Other recent studies have demonstrated the advantage of WGS in investigating community outbreaks over the conventional methods and this is important for optimising local or international control measures(125)(126)(127)(128).…”

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Application of whole genome sequencing to characterize Mycobacterium tuberculosis strains circulating in Far North Queensland, Australia and Western Province, Papua New Guinea

Bainomugisa¹

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Mycobacterium tuberculosis (MTB) is an obligate intracellular human pathogen that causes tuberculosis (TB) disease. Today, TB is the leading cause of death from a single infectious agent and ninth leading cause of death globally. Increasing burden of drug-resistant TB is threatening the achievements and targets set by World Health Organisation (WHO). With the recent advances in whole genome sequencing (WGS) technology, there is renewed hope for its role as a 'game changer' towards eliminating TB. This thesis focusses on the utility of WGS technology on MTB strains circulating in Far North Queensland (Australia) and Western Province (Papua New Guinea) for extensive understanding of molecular epidemiology and evolutionary dynamics that are important for improved TB management. Western Province, Papua New Guinea (PNG) which neighbours Far North Queensland has one of the highest numbers of drug resistant TB globally. Various efforts are V Publications included in this thesis 1. Coulter and Lachlan J. M. Coin. Multi-clonal evolution of MDR/XDR M. tuberculosis in a high prevalence setting in Papua New Guinea over three decades. Marais and Lachlan M. Coin. A complete high-quality MinION nanopore assembly of an extensively drug-resistant Mycobacterium tuberculosis Beijing lineage strain identifies novel variation in repetitive PE/PPE gene regions.

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Author response: Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area

Cited by 5 publications

References 0 publications

Population structure and transmission ofMycobacterium bovisin Ethiopia

Population structure and transmission ofMycobacterium bovisin Ethiopia

Molecular epidemiology of drug resistant Mycobacterium tuberculosis in Africa: a systematic review

Application of whole genome sequencing to characterize Mycobacterium tuberculosis strains circulating in Far North Queensland, Australia and Western Province, Papua New Guinea

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