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
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TLDR
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.Abstract:
The molecular mechanisms determining the transmissibility and prevalence of drug-resistant tuberculosis in a population were investigated through whole-genome sequencing of 1,000 prospectively obtained patient isolates from Russia. Two-thirds belonged to the Beijing lineage, which was dominated by two homogeneous clades. Multidrug-resistant (MDR) genotypes were found in 48% of isolates overall and in 87% of the major clades. The most common rpoB mutation was associated with fitness-compensatory mutations in rpoA or rpoC, and a new intragenic compensatory substitution was identified. The proportion of MDR cases with extensively drug-resistant (XDR) tuberculosis was 16% overall, with 65% of MDR isolates harboring eis mutations, selected by kanamycin therapy, which may drive the expansion of strains with enhanced virulence. 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.read more
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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
Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis
TL;DR: The analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes that suggest a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors.
Journal ArticleDOI
A robust SNP barcode for typing Mycobacterium tuberculosis complex strains.
Francesc Coll,Ruth McNerney,José Afonso Guerra-Assunção,Judith R. Glynn,João Perdigão,Miguel Viveiros,Isabel Portugal,Arnab Pain,Nigel Martin,Taane G. Clark +9 more
TL;DR: This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives, and may be used to classify clinical isolates to evaluate tools to control the disease.
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
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.
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