Open Access
Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis
Maha R. Farhat,B. Jesse Shapiro,Karen J. Kieser,Razvan Sultana,Karen R. Jacobson,Karen R. Jacobson,Thomas C. Victor,Robin M. Warren,Elizabeth M. Streicher,Alistair Calver,Alexander Sloutsky,Devinder Kaur,Jamie E. Posey,Bonnie B. Plikaytis,Marco R. Oggioni,Jennifer L. Gardy,James C. Johnston,Mabel Rodrigues,Patrick Tang,Midori Kato-Maeda,Mark L. Borowsky,Bhavana Muddukrishna,Barry N. Kreiswirth,Natalia Kurepina,James E. Galagan,Sebastien Gagneux,Sebastien Gagneux,Bruce W. Birren,Eric J. Rubin,Eric S. Lander,Pardis C. Sabeti,Megan Murray +31 more
Reads0
Chats0
TLDR
In this article, the authors identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains of M. tuberculosis and identified positive selection in 39 genomic regions in resistant isolates, encoding components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways.Abstract:
M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution--the independent fixation of mutations in the same nucleotide position or gene--we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin.read more
Citations
More filters
Journal ArticleDOI
Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study.
Timothy M Walker,Thomas Kohl,Shaheed V. Omar,Jessica Hedge,Carlos del Ojo Elias,Phelim Bradley,Zamin Iqbal,Silke Feuerriegel,Katherine E. Niehaus,Daniel J. Wilson,David A. Clifton,Georgia Kapatai,Camilla L. C. Ip,Rory Bowden,Francis Drobniewski,Francis Drobniewski,Caroline Allix-Béguec,Cyril Gaudin,Julian Parkhill,Roland Diel,Philip Supply,Philip Supply,Derrick W. Crook,E. Grace Smith,A. Sarah Walker,Nazir Ahmed Ismail,Stefan Niemann,Tim E. A. Peto +27 more
TL;DR: A broad catalogue of genetic mutations enable data from whole-genome sequencing to be used clinically to predict drug resistance, drug susceptibility, or to identify drug phenotypes that cannot yet be genetically predicted.
Journal ArticleDOI
The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis
Keertan Dheda,Tawanda Gumbo,Gary Maartens,Kelly E. Dooley,Ruth McNerney,Megan Murray,Jennifer Furin,Edward A. Nardell,Leslie London,Erica Lessem,Grant Theron,Paul D. van Helden,Stefan Niemann,Matthias Merker,David W. Dowdy,Annelies Van Rie,Annelies Van Rie,Gilman Kit Hang Siu,Jotam G. Pasipanodya,Camilla Rodrigues,Taane G. Clark,F. A. Sirgel,Aliasgar Esmail,Hsien-Ho Lin,Sachin R Atre,H. Simon Schaaf,Kwok Chiu Chang,Christoph Lange,Payam Nahid,Zarir F Udwadia,C. Robert Horsburgh,Gavin J. Churchyard,Gavin J. Churchyard,Dick Menzies,Anneke C. Hesseling,Eric L. Nuermberger,Helen McIlleron,Kevin P. Fennelly,Eric Goemaere,Ernesto Jaramillo,Marcus Low,Carolina Morán Jara,Nesri Padayatchi,Robin M. Warren +43 more
TL;DR: Several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis.
Journal ArticleDOI
Evolution and transmission of drug-resistant tuberculosis in a Russian population
Nicola Casali,Vladyslav Nikolayevskyy,Yanina Balabanova,Simon R. Harris,Olga Ignatyeva,Irina Kontsevaya,Jukka Corander,Josephine M. Bryant,Julian Parkhill,Sergey Nejentsev,Rolf D. Horstmann,Tim Brown,Francis Drobniewski +12 more
TL;DR: The combination of drug resistance and compensatory mutations displayed by the major clades confers clinical resistance without compromising fitness and transmissibility, showing that, in addition to weaknesses in the tuberculosis control program, biological factors drive the persistence and spread of MDR and XDR tuberculosis in Russia and beyond.
Journal ArticleDOI
Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage
Matthias Merker,Camille Blin,Stefano Mona,Nicolas Duforet-Frebourg,Sophie Lecher,Eve Willery,Michael G. B. Blum,Sabine Rüsch-Gerdes,Igor Mokrousov,Eman Aleksic,Caroline Allix-Béguec,Annick Antierens,Ewa Augustynowicz-Kopeć,Marie Ballif,Francesca Barletta,Hans P eter Beck,Clifton E. Barry,Maryline Bonnet,Emanuele Borroni,Isolina Campos-Herrero,Daniela Maria Cirillo,Helen Cox,Suzanne M. Crowe,Valeriu Crudu,Roland Diel,Francis Drobniewski,Maryse Fauville-Dufaux,Sebastien Gagneux,Solomon Ghebremichael,Madeleine Hanekom,Sven Hoffner,Wei wei Jiao,Stobdan Kalon,Thomas Kohl,Irina Kontsevaya,Troels Lillebaek,Shinji Maeda,Vladyslav Nikolayevskyy,Michael Rasmussen,Nalin Rastogi,Sofía Samper,Elisabeth Sanchez-Padilla,Branislava Savic,Isdore Chola Shamputa,Adong Shen,Li Hwei Sng,Petras Stakenas,Kadri Toit,Francis Varaine,Dragana Vuković,Céline Wahl,Robin M. Warren,Philip Supply,Stefan Niemann,Thierry Wirth +54 more
TL;DR: It is shown that this lineage of mycobacterium tuberculosis strains of the Beijing lineage initially originated in the Far East, from where it radiated worldwide in several waves and detected successive increases in population size over the last 200 years.
Journal ArticleDOI
Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary.
TL;DR: Scoary is introduced, an ultra-fast, easy-to-use, and widely applicable software tool that scores the components of the pan-genome for associations to observed phenotypic traits while accounting for population stratification, with minimal assumptions about evolutionary processes.
References
More filters
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Journal ArticleDOI
MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice across a Large Model Space
Fredrik Ronquist,Maxim Teslenko,Paul van der Mark,Daniel L. Ayres,Aaron E. Darling,Sebastian Höhna,Bret Larget,Liang Liu,Marc A. Suchard,John P. Huelsenbeck +9 more
TL;DR: The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly, and provides more output options than previously, including samples of ancestral states, site rates, site dN/dS rations, branch rates, and node dates.
Journal ArticleDOI
New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0
Stéphane Guindon,Jean-François Dufayard,Vincent Lefort,Maria Anisimova,Wim Hordijk,Olivier Gascuel +5 more
TL;DR: A new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves and a new test to assess the support of the data for internal branches of a phylogeny are introduced.
Journal ArticleDOI
Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows
TL;DR: The main innovations of the new version of the Arlequin program include enhanced outputs in XML format, the possibility to embed graphics displaying computation results directly into output files, and the implementation of a new method to detect loci under selection from genome scans.
Journal ArticleDOI
Circos: An information aesthetic for comparative genomics
Martin Krzywinski,Jacqueline E. Schein,Inanc Birol,Joseph M. Connors,Randy D. Gascoyne,Doug Horsman,Steven J.M. Jones,Marco A. Marra +7 more
TL;DR: Circos uses a circular ideogram layout to facilitate the display of relationships between pairs of positions by the use of ribbons, which encode the position, size, and orientation of related genomic elements.