Whole Genome Sequencing versus Traditional Genotyping for Investigation of a Mycobacterium tuberculosis Outbreak: A Longitudinal Molecular Epidemiological Study
Andreas Roetzer,Roland Diel,Thomas Kohl,Christian Rückert,Ulrich Nübel,Jochen Blom,Thierry Wirth,Sebastian Jaenicke,Sieglinde Schuback,Sabine Rüsch-Gerdes,Philip Supply,Jörn Kalinowski,Stefan Niemann +12 more
TLDR
In an outbreak investigation of Mycobacterium tuberculosis comparing whole genome sequencing (WGS) with traditional genotyping, Stefan Niemann and colleagues found that classical genotypes falsely clustered some strains, and WGS better reflected contact tracing.Abstract:
Background: Understanding Mycobacterium tuberculosis (Mtb) transmission is essential to guide efficient tuberculosis control strategies. Traditional strain typing lacks sufficient discriminatory power to resolve large outbreaks. Here, we tested the potential of using next generation genome sequencing for identification of outbreak-related transmission chains. Methods and Findings: During long-term (1997 to 2010) prospective population-based molecular epidemiological surveillance comprising a total of 2,301 patients, we identified a large outbreak caused by an Mtb strain of the Haarlem lineage. The main performance outcome measure of whole genome sequencing (WGS) analyses was the degree of correlation of the WGS analyses with contact tracing data and the spatio-temporal distribution of the outbreak cases. WGS analyses of the 86 isolates revealed 85 single nucleotide polymorphisms (SNPs), subdividing the outbreak into seven genome clusters (two to 24 isolates each), plus 36 unique SNP profiles. WGS results showed that the first outbreak isolates detected in 1997 were falsely clustered by classical genotyping. In 1998, one clone (termed ‘‘Hamburg clone’’) started expanding, apparently independently from differences in the social environment of early cases. Genome-based clustering patterns were in better accordance with contact tracing data and the geographical distribution of the cases than clustering patterns based on classical genotyping. A maximum of three SNPs were identified in eight confirmed human-to-human transmission chains, involving 31 patients. We estimated the Mtb genome evolutionary rate at 0.4 mutations per genome per year. This rate suggests that Mtb grows in its natural host with a doubling time of approximately 22 h (400 generations per year). Based on the genome variation discovered, emergence of the Hamburg clone was dated back to a period between 1993 and 1997, hence shortly before the discovery of the outbreak through epidemiological surveillance. Conclusions: Our findings suggest that WGS is superior to conventional genotyping for Mtb pathogen tracing and investigating micro-epidemics. WGS provides a measure of Mtb genome evolution over time in its natural host context. Please see later in the article for the Editors’ Summary.read more
Citations
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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.
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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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Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015
Henrik Hasman,Anette M. Hammerum,Frank Hansen,Rene S. Hendriksen,Bente Olesen,Yvonne Agersø,Ea Zankari,Pimlapas Leekitcharoenphon,Marc Stegger,Rolf Sommer Kaas,Lina Cavaco,Dennis S. Hansen,Frank Møller Aarestrup,Robert Skov +13 more
TL;DR: The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat.
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Molecular epidemiology of tuberculosis.
Peter F. Barnes,M. Donald Cave +1 more
TL;DR: The ability to determine the genotype of Mycobacterium tuberculosis is changing our understanding of the dynamics of tuberculosis transmission as discussed by the authors, and a review summarizes the methods of genotyping and...
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The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria : report from the EUCAST Subcommittee
Matthew J. Ellington,Oskar Ekelund,Frank Møller Aarestrup,Rafael Cantón,Michel Doumith,Christian G. Giske,H. Grundman,Henrik Hasman,Matthew T. G. Holden,Katie L. Hopkins,J. Iredell,Gunnar Kahlmeter,Claudio U. Köser,Alasdair P. MacGowan,Dik Mevius,Dik Mevius,Michael R. Mulvey,Thierry Naas,Tim E. A. Peto,J.-M. Rolain,Ørjan Samuelsen,Neil Woodford +21 more
TL;DR: The European Committee on Antimicrobial Susceptibility Testing established a subcommittee to review the current development status of Whole Genome Sequencing (WGS) for bacterial antimicrobial susceptibility testing (AST) as discussed by the authors.
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