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

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

doi:10.24072/pcjournal.307

Peer Community Journal (Aug 2023)

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

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

Affiliations

Hennart, Mélanie: ORCiD; Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France; Sorbonne Université, Collège doctoral, F-75005 Paris, France
Crestani, Chiara: ORCiD; Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France
Bridel, Sébastien: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France
Armatys, Nathalie: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Brémont, Sylvie: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Carmi-Leroy, Annick: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Landier, Annie: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Passet, Virginie: Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Fonteneau, Laure: Santé publique France, Saint-Maurice, France
Vaux, Sophie: ORCiD; Santé publique France, Saint-Maurice, France
Toubiana, Julie: ORCiD; Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université de Paris, Paris, France
Badell, Edgar: ORCiD; Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France
Brisse, Sylvain: ORCiD; Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, F-75015, Paris, France; Institut Pasteur, National Reference Center for Corynebacteria of the Diphtheriae Complex, Paris, France

DOI: https://doi.org/10.24072/pcjournal.307
Journal volume & issue: Vol. 3

Abstract

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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 https://gitlab.pasteur.fr/BEBP/diphtoscan) 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.

diphtheria, genomic sequencing, antimicrobial resistance, virulence, epidemiology, transmission, 2022 reemergence, bioinformatics tool

Published in Peer Community Journal

ISSN: 2804-3871 (Online)
Publisher: Peer Community In
Country of publisher: France
LCC subjects: Auxiliary sciences of history: Archaeology; Science
Website: https://peercommunityjournal.org/

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