%0 Journal Article %T Genomic epidemiology and strain taxonomy of Corynebacterium diphtheriae %+ Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB %+ Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens %+ Collège Doctoral %+ 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] %+ Département de Biologie Computationnelle - Department of Computational Biology %A Guglielmini, Julien %A Hennart, Melanie %A Badell, Edgar %A Toubiana, Julie %A Criscuolo, Alexis %A Brisse, Sylvain %Z 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 %Z 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 %< avec comité de lecture %@ 0095-1137 %J Journal of Clinical Microbiology %I American Society for Microbiology %P JCM0158121 %8 2021-09-16 %D 2021 %R 10.1128/jcm.01581-21 %M 34524891 %Z Life Sciences [q-bio]Journal articles %X Background Corynebacterium diphtheriae is 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 of C. diphtheriae are not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. Methods We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST genes diversity among 602 isolates from sporadic clinical cases, small clusters or large outbreaks. We defined sublineages based on the phylogenetic structure within C. diphtheriae and strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. Results The cgMLST scheme showed high allele call rate in C. diphtheriae and the closely related species C. belfantii and C. 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 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 mismatches 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 at https://bigsdb.pasteur.fr/diphtheria . Conclusions Standardized genome-scale strain genotyping will help tracing transmission and geographic spread of C. diphtheriae . The unified genomic taxonomy of C. diphtheriae strains provides a common language for studies into the ecology, evolution and virulence heterogeneity among C. diphtheriae sublineages. %G English %Z 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 %2 https://pasteur.hal.science/pasteur-03346634/document %2 https://pasteur.hal.science/pasteur-03346634/file/Genomic%20epidemiology%20and%20strain%20taxonomy%20of%20Corynebacterium%20diphtheriae.pdf %L pasteur-03346634 %U https://pasteur.hal.science/pasteur-03346634 %~ PASTEUR %~ APHP %~ OPENAIRE %~ CHU-UNIV-PARIS5 %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ SU-TI %~ ANR %~ ALLIANCE-SU %~ FRANCE-GENOMIQUE %~ BIOINFO_BIOSTAT_HUB