Genomic epidemiology and strain taxonomy of Corynebacterium diphtheriae

Autor: Edgar Badell, Julie Toubiana, Melanie Hennart, Sylvain Brisse, Alexis Criscuolo, Julien Guglielmini
Přispěvatelé: Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Collège Doctoral, Sorbonne Université (SU), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biologie Computationnelle - Department of Computational Biology, This research was funded, in whole or in part, by Institut Pasteur and Santé publique France. For the purpose of open access, the authors have applied a CC-BY public copyright license to any Author Manuscript version arising from this submission, Received financial support from the French Government Investissement d’Avenir Programme Laboratoire d’Excellence on Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID). M.H. was supported financially by a PhD grant from the European Joint Programme One Health, which has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 570773830, We thank Melody Dazasfor assistance in the early steps of the project and Annick Carmi-Leroy, Annie Landier, Nathalie Armatys and Virginie Passet for technical assistance with the microbiological characterization and sequencing of the Corynebacterium diphtheriaestrains from the National Reference Center. We thank Vincent Enouf and the P2M core facility of Institut Pasteur for genomic sequencing. This work used the computational and storage services (TARS cluster) provided by the IT department at the Institut Pasteur, Paris, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Clinical Microbiology
Journal of Clinical Microbiology, 2021, pp.JCM0158121. ⟨10.1128/jcm.01581-21⟩
J Clin Microbiol
Journal of Clinical Microbiology, American Society for Microbiology, 2021, pp.JCM0158121. ⟨10.1128/jcm.01581-21⟩
ISSN: 0095-1137
Popis: Corynebacterium diphtheriaeis highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution ofC. diphtheriaeare not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST gene diversity among 602 isolates from sporadic clinical cases, small clusters, or large outbreaks. We defined sublineages based on the phylogenetic structure withinC. diphtheriaeand strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. The cgMLST scheme showed high allele call rate inC. diphtheriaeand the closely related speciesC. belfantiiandC. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed a short-timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500-cgMLST-mismatch threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible (https://bigsdb.pasteur.fr/diphtheria). Standardized genome-scale strain genotyping will help tracing transmission and geographic spread ofC. diphtheriae. The unified genomic taxonomy ofC. diphtheriaestrains provides a common language for studies of ecology, evolution, and virulence heterogeneity amongC. diphtheriaesublineages.
Databáze: OpenAIRE
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