A global Corynebacterium diphtheriae genomic framework sheds light on current diphtheria reemergence

10.24072/pcjournal.307 - Peer Community Journal, Volume 3 (2023), article no. e76.

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Background: Diphtheria, caused by Corynebacterium diphtheriae, reemerges in Europe since 2022. Genomic sequencing can inform on transmission routes and genotypes of concern, but currently, no standard approach exists to detect clinically important genomic features and to interpret emergence in the global C. diphtheriae population framework. Methods: We developed the bioinformatics pipeline diphtOscan (available at to extract from genomes of Corynebacteria of the diphtheriae species complex, medically relevant features including tox gene presence and disruption. We analyzed 101 human C. diphtheriae isolates collected in 2022 in metropolitan and overseas France (France-2022). To define the population background of this emergence, we sequenced 379 additional isolates (mainly from France, 2018-2021) and collated 870 publicly-available genomes. Results: The France-2022 isolates comprised 45 tox-positive (44 toxigenic) isolates, mostly imported, belonging to 10 sublineages (<500 distinct core genes). The global dataset comprised 245 sublineages and 33.9% tox-positive genomes, with diphtOscan predicting non-toxigenicity in 16.0% of these. 12% of the global isolates, and 43.6% of France-2022 ones, were multidrug resistant. Convergence of toxigenicity with penicillin and erythromycin resistance was observed in 2 isolates from France-2022. Phylogenetic lineages Gravis and Mitis contrasted strikingly in their pathogenicity-associated genes. Conclusions: This work provides a bioinformatics tool and global population framework to analyze C. diphtheriae genomes, revealing important heterogeneities in virulence and resistance features. Emerging genotypes combining toxigenicity and first-line antimicrobial resistance represent novel threats. Genomic epidemiology studies of C. diphtheriae should be intensified globally to improve understanding of reemergence and spatial spread.

Published online:
DOI: 10.24072/pcjournal.307
Keywords: diphtheria, genomic sequencing, antimicrobial resistance, virulence, epidemiology, transmission, 2022 reemergence, bioinformatics tool
Hennart, Mélanie 1, 2, 3; Crestani, Chiara 1; Bridel, Sébastien 1; Armatys, Nathalie 1, 2; Brémont, Sylvie 1, 2; Carmi-Leroy, Annick 1, 2; Landier, Annie 1, 2; Passet, Virginie 1, 2; Fonteneau, Laure 4; Vaux, Sophie 4; Toubiana, Julie 1, 2, 5; Badell, Edgar 1, 2; Brisse, Sylvain 1, 2

1 Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France
2 Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
3 Sorbonne Université, Collège doctoral, F-75005 Paris, France
4 Santé publique France, Saint-Maurice, France
5 Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université de Paris, Paris, France
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights
     author = {Hennart, M\'elanie and Crestani, Chiara and Bridel, S\'ebastien and Armatys, Nathalie and Br\'emont, Sylvie and Carmi-Leroy, Annick and Landier, Annie and Passet, Virginie and Fonteneau, Laure and Vaux, Sophie and Toubiana, Julie and Badell, Edgar and Brisse, Sylvain},
     title = {A global {\protect\emph{Corynebacterium} diphtheriae} genomic framework sheds light on current diphtheria reemergence},
     journal = {Peer Community Journal},
     eid = {e76},
     publisher = {Peer Community In},
     volume = {3},
     year = {2023},
     doi = {10.24072/pcjournal.307},
     language = {en},
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AU  - Crestani, Chiara
AU  - Bridel, Sébastien
AU  - Armatys, Nathalie
AU  - Brémont, Sylvie
AU  - Carmi-Leroy, Annick
AU  - Landier, Annie
AU  - Passet, Virginie
AU  - Fonteneau, Laure
AU  - Vaux, Sophie
AU  - Toubiana, Julie
AU  - Badell, Edgar
AU  - Brisse, Sylvain
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%A Hennart, Mélanie
%A Crestani, Chiara
%A Bridel, Sébastien
%A Armatys, Nathalie
%A Brémont, Sylvie
%A Carmi-Leroy, Annick
%A Landier, Annie
%A Passet, Virginie
%A Fonteneau, Laure
%A Vaux, Sophie
%A Toubiana, Julie
%A Badell, Edgar
%A Brisse, Sylvain
%T A global Corynebacterium diphtheriae genomic framework sheds light on current diphtheria reemergence
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Hennart, Mélanie; Crestani, Chiara; Bridel, Sébastien; Armatys, Nathalie; Brémont, Sylvie; Carmi-Leroy, Annick; Landier, Annie; Passet, Virginie; Fonteneau, Laure; Vaux, Sophie; Toubiana, Julie; Badell, Edgar; Brisse, Sylvain. A global Corynebacterium diphtheriae genomic framework sheds light on current diphtheria reemergence. Peer Community Journal, Volume 3 (2023), article  no. e76. doi : 10.24072/pcjournal.307.

Peer reviewed and recommended by PCI : 10.24072/pci.infections.100080

Conflict of interest of the recommender and peer reviewers:
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

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