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Article ; Online: Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis.

Joshua L Payne / Fabrizio Menardo / Andrej Trauner / Sonia Borrell / Sebastian M Gygli / Chloe Loiseau / Sebastien Gagneux / Alex R Hall

PLoS Biology, Vol 17, Iss 5, p e

2019 Volume 3000265

Abstract: Transition bias, an overabundance of transitions relative to transversions, has been widely reported among studies of the rates and spectra of spontaneous mutations. However, demonstrating the role of transition bias in adaptive evolution remains ... ...

Abstract	Transition bias, an overabundance of transitions relative to transversions, has been widely reported among studies of the rates and spectra of spontaneous mutations. However, demonstrating the role of transition bias in adaptive evolution remains challenging. In particular, it is unclear whether such biases direct the evolution of bacterial pathogens adapting to treatment. We addressed this challenge by analyzing adaptive antibiotic-resistance mutations in the major human pathogen Mycobacterium tuberculosis (MTB). We found strong evidence for transition bias in two independently curated data sets comprising 152 and 208 antibiotic-resistance mutations. This was true at the level of mutational paths (distinct adaptive DNA sequence changes) and events (individual instances of the adaptive DNA sequence changes) and across different genes and gene promoters conferring resistance to a diversity of antibiotics. It was also true for mutations that do not code for amino acid changes (in gene promoters and the 16S ribosomal RNA gene rrs) and for mutations that are synonymous to each other and are therefore likely to have similar fitness effects, suggesting that transition bias can be caused by a bias in mutation supply. These results point to a central role for transition bias in determining which mutations drive adaptive antibiotic resistance evolution in a key pathogen.
Keywords	Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 11

Abstract: Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia ... ...

Abstract	Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDR-TB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDR-TB hotspots.
Keywords	Science ; Q
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tuberculosis in Swiss captive Asian elephants

Giovanni Ghielmetti / Mireia Coscolla / Maja Ruetten / Ute Friedel / Chloé Loiseau / Julia Feldmann / Hanspeter W. Steinmetz / David Stucki / Sebastien Gagneux

Scientific Reports, Vol 7, Iss 1, Pp 1-

microevolution of Mycobacterium tuberculosis characterized by multilocus variable-number tandem-repeat analysis and whole-genome sequencing

2017 Volume 8

Abstract: Abstract Zoonotic tuberculosis is a risk for human health, especially when animals are in close contact with humans. Mycobacterium tuberculosis was cultured from several organs, including lung tissue and gastric mucosa, of three captive elephants ... ...

Abstract	Abstract Zoonotic tuberculosis is a risk for human health, especially when animals are in close contact with humans. Mycobacterium tuberculosis was cultured from several organs, including lung tissue and gastric mucosa, of three captive elephants euthanized in a Swiss zoo. The elephants presented weight loss, weakness and exercise intolerance. Molecular characterization of the M. tuberculosis isolates by spoligotyping revealed an identical profile, suggesting a single source of infection. Multilocus variable-number of tandem-repeat analysis (MLVA) elucidated two divergent populations of bacteria and mixed infection in one elephant, suggesting either different transmission chains or prolonged infection over time. A total of eight M. tuberculosis isolates were subjected to whole-genome sequence (WGS) analysis, confirming a single source of infection and indicating the route of transmission between the three animals. Our findings also show that the methods currently used for epidemiological investigations of M. tuberculosis infections should be carefully applied on isolates from elephants. Moreover the importance of multiple sampling and analysis of within-host mycobacterial clonal populations for investigations of transmission is demonstrated.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reference set of Mycobacterium tuberculosis clinical strains

Sònia Borrell / Andrej Trauner / Daniela Brites / Leen Rigouts / Chloe Loiseau / Mireia Coscolla / Stefan Niemann / Bouke De Jong / Dorothy Yeboah-Manu / Midori Kato-Maeda / Julia Feldmann / Miriam Reinhard / Christian Beisel / Sebastien Gagneux

PLoS ONE, Vol 14, Iss 3, p e

A tool for research and product development.

2019 Volume 0214088

Abstract: The Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and various other mammals. The human-adapted members of the MTBC comprise seven phylogenetic lineages that differ in their geographical distribution. There is growing ... ...

Abstract	The Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and various other mammals. The human-adapted members of the MTBC comprise seven phylogenetic lineages that differ in their geographical distribution. There is growing evidence that this phylogeographic diversity modulates the outcome of TB infection and disease. For decades, TB research and development has focused on the two canonical MTBC laboratory strains H37Rv and Erdman, both of which belong to Lineage 4. Relying on only a few laboratory-adapted strains can be misleading as study results might not be directly transferrable to clinical settings where patients are infected with a diverse array of strains, including drug-resistant variants. Here, we argue for the need to expand TB research and development by incorporating the phylogenetic diversity of the MTBC. To facilitate such work, we have assembled a group of 20 genetically well-characterized clinical strains representing the seven known human-adapted MTBC lineages. With the "MTBC clinical strains reference set" we aim to provide a standardized resource for the TB community. We hope it will enable more direct comparisons between studies that explore the physiology of MTBC beyond the laboratory strains used thus far. We anticipate that detailed phenotypic analyses of this reference strain set will increase our understanding of TB biology and assist in the development of new control tools that are broadly effective.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana

Prince Asare / Isaac Darko Otchere / Edmund Bedeley / Daniela Brites / Chloé Loiseau / Nyonuku Akosua Baddoo / Adwoa Asante-Poku / Stephen Osei-Wusu / Diana Ahu Prah / Sonia Borrell / Miriam Reinhard / Audrey Forson / Kwadwo Ansah Koram / Sebastien Gagneux / Dorothy Yeboah-Manu

Frontiers in Medicine, Vol

2020 Volume 7

Abstract: Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of ... ...

Abstract	Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4–12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.
Keywords	Mycobacterium tuberculosis ; Mycobacterium africanum ; molecular epidemiology ; whole genome sequence ; recent transmission ; cluster ; Medicine (General) ; R5-920
Subject code	572
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treemmer

Fabrizio Menardo / Chloé Loiseau / Daniela Brites / Mireia Coscolla / Sebastian M. Gygli / Liliana K. Rutaihwa / Andrej Trauner / Christian Beisel / Sonia Borrell / Sebastien Gagneux

BMC Bioinformatics, Vol 19, Iss 1, Pp 1-

a tool to reduce large phylogenetic datasets with minimal loss of diversity

2018 Volume 8

Abstract: Abstract Background Large sequence datasets are difficult to visualize and handle. Additionally, they often do not represent a random subset of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer ...

Abstract	Abstract Background Large sequence datasets are difficult to visualize and handle. Additionally, they often do not represent a random subset of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases. Results Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity. Conclusions Treemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity. Additionally, it is possible to fine-tune the behavior of Treemmer including any kind of meta-information, making Treemmer particularly useful for empirical studies.
Keywords	Representative sample ; Large phylogenetic trees ; Redundancy reduction ; Size reduction ; Sampling bias ; Clone elimination ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing

Kathrin Zürcher, MSc / Martina L Reichmuth, MSc / Marie Ballif, PhD / Chloé Loiseau, PhD / Sonia Borrell, PhD / Miriam Reinhard / Veronika Skrivankova, PhD / Rico Hömke / Peter Sander, MD / Anchalee Avihingsanon, MD / Alash'le G Abimiku, ProfPhD / Olivier Marcy, MD / Jimena Collantes, MSc / E Jane Carter, MD / Robert J Wilkinson, ProfPhD / Helen Cox, ProfPhD / Marcel Yotebieng, ProfMD / Robin Huebner, PhD / Lukas Fenner, ProfMD /

Erik C Böttger, ProfMD / Sebastien Gagneux, ProfPhD / Matthias Egger, ProfMD

The Lancet Microbe, Vol 2, Iss 7, Pp e320-e

a multicentre cohort study

2021 Volume 330

Abstract: Summary: Background: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done ... ...

Abstract	Summary: Background: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS). Methods: In this multicentre cohort study, we collected pulmonary Mycobacterium tuberculosis isolates and clinical data from individuals with tuberculosis from antiretroviral therapy programmes and tuberculosis clinics in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, Peru, South Africa, and Thailand, stratified by HIV status and drug resistance. Sites tested drug susceptibility using routinely available methods. WGS was done on Illumina HiSeq 2500 in the USA and Switzerland, and TBprofiler was used to analyse the genomes. We included individuals aged 16 years or older with pulmonary tuberculosis (bacteriologically confirmed or clinically diagnosed). We analysed mortality in multivariable logistic regression models adjusted for sex, age, HIV status, history of tuberculosis, and sputum positivity. Findings: Between Sept 1, 2014, and July 4, 2016, of 634 patients included in our previous analysis, we included 582 patients with tuberculosis (median age 33 years [IQR 27–43], 225 [39%] women, and 247 [42%] HIV-positive). Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-extensively drug-resistant (pre-XDR) or XDR. The analysis of mortality was based on 530 patients; 63 (12%) died and 77 (15%) patients received inappropriate treatment. Mortality ranged from 6% (18 of 310) in patients with pan-susceptible tuberculosis to 39% (nine of 23) in patients with pre-XDR or XDR tuberculosis. The adjusted odds ratio for mortality was 4·92 (95% CI 2·47–9·78) among undertreated patients, compared with appropriately treated patients. Interpretation: In seven countries with a high burden of tuberculosis, we observed discrepancies between drug ...
Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Subject code	610 ; 310
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

Jean Claude Semuto Ngabonziza / Chloé Loiseau / Michael Marceau / Agathe Jouet / Fabrizio Menardo / Oren Tzfadia / Rudy Antoine / Esdras Belamo Niyigena / Wim Mulders / Kristina Fissette / Maren Diels / Cyril Gaudin / Stéphanie Duthoy / Willy Ssengooba / Emmanuel André / Michel K. Kaswa / Yves Mucyo Habimana / Daniela Brites / Dissou Affolabi /

Jean Baptiste Mazarati / Bouke Catherine de Jong / Leen Rigouts / Sebastien Gagneux / Conor Joseph Meehan / Philip Supply

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract: The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to be evolved from a common progenitor in Africa. Here, the authors identify two MTBC strains isolated from patients with multidrug-resistant tuberculosis, ...

Abstract	The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to be evolved from a common progenitor in Africa. Here, the authors identify two MTBC strains isolated from patients with multidrug-resistant tuberculosis, representing an as-yet-unknown lineage further supporting an East African origin for the MTBC.
Keywords	Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region

Jean Baptiste Mazarati / Bouke Catherine de Jong / Leen Rigouts / Sebastien Gagneux / Conor Joseph Meehan / Philip Supply

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract	The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to be evolved from a common progenitor in Africa. Here, the authors identify two MTBC strains isolated from patients with multidrug-resistant tuberculosis, representing an as-yet-unknown lineage further supporting an East African origin for the MTBC.
Keywords	Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim [version 1; peer review

Fabrizio Menardo / Liliana K. Rutaihwa / Michaela Zwyer / Sonia Borrell / Iñaki Comas / Emilyn Costa Conceição / Mireia Coscolla / Helen Cox / Moses Joloba / Horng-Yunn Dou / Julia Feldmann / Lukas Fenner / Janet Fyfe / Qian Gao / Darío García de Viedma / Alberto L. Garcia-Basteiro / Sebastian M. Gygli / Jerry Hella / Hellen Hiza /

F1000Research, Vol

2 approved]

2021 Volume 10

Abstract: Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new ... ...

Abstract	Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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