A global<i>Corynebacterium diphtheriae</i>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:10.1101/2023.02.20.529124

Cited by 3 publications

(5 citation statements)

References 74 publications

(119 reference statements)

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“…The latest version of the diphtOscan code will be available at https://gitlab.pasteur.fr/BEBP/diphtoscan and the version used in this work is available at: https://doi.org/10.5281/zenodo.10.5281/zenodo.8121098 (Hennart, 2023a).…”

Section: Fundingmentioning

confidence: 99%

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

Hennart,

Crestani,

Bridel

et al. 2023

Peer Community Journal

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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 pathogenicityassociated 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.

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Section: Fundingmentioning

confidence: 99%

“…The trees are available at https://itol.embl.de/shared/Pasteur_BEBP in the projet: 'Hennart et al, 2023: diphtOscan'. This manuscript contains a supplementary file with figures S1 to S10. Supplementary tables S1 to S5 are also part of this manuscript (Hennart, 2023b; https://doi.org/10.5281/zenodo.8123234).…”

Section: Fundingmentioning

confidence: 99%

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

Hennart,

Crestani,

Bridel

et al. 2023

Peer Community Journal

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“…It is noteworthy that in contrast to the fluoroquinolone-resistant nontoxigenic C. diphtheriae strain FRC0074 from a cystic fibrosis patient [45], which contained the deduced amino acid change D91N within gyrA , all eight strains in this study were phenotypically either I (susceptible, increased exposure) or resistant, and all contained the deduced amino acid change D93A mutation also linked to fluoroquinolone resistance [46]. Furthermore the isolate 717086 (from case 2), which exhibited the highest MIC value of >32 for ciprofloxacin, also contained a S89A mutation previously linked to ciprofloxacin resistance [47].…”

Section: Resultsmentioning

confidence: 99%

“…The isolate from case 2 and isolates 4b and 4c from case 4 were resistant to ciprofloxacin, whereas ciprofloxacin MICs for all other isolates were interpreted as susceptible, increased exposure. However, genomic analysis indicated all eight strains contained the D93A mutation within gyrA previously linked to fluoroquinolone resistance [46]. Isolate 717 086 from case 2, which exhibited the highest MIC value of >32 for ciprofloxacin, also contained a S89A mutation that has been linked to ciprofloxacin resistance [47].…”

Section: Resultsmentioning

confidence: 99%

Household transmission of non-toxigenic diphtheria toxin gene-bearing Corynebacterium diphtheriae following a cluster of cutaneous cases in a specialist outpatient setting

Fry,

Pringle,

Newsholme

et al. 2023

Journal of Medical Microbiology

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Introduction. Combination of PCR and Elek testing to identify toxigenic corynebacteria has revealed organisms described as non-toxigenic toxin-gene bearing (NTTB) Corynebacterium diphtheriae or C. ulcerans (i.e. PCR tox positive; Elek negative). These organisms carry part or all of tox, but are unable to express diphtheria toxin (DT) and present a challenge to clinical and public health case management. Gap analysis/Hypothesis. There are few data on the theoretical risk of NTTB reversion to toxigenicity. This unique cluster and subsequent epidemiologically linked isolates allowed the opportunity to determine any change in DT expression status. Aim. To characterize a cluster of infections due to NTTB in a skin clinic and subsequent cases in two household contacts. Methodology. Epidemiological and microbiological investigations were carried out according to existing national guidance at the time. Susceptibility testing used gradient strips. The tox operon analysis and multi-locus sequence typing (MLST) was derived from whole-genome sequencing. Alignment of the tox operon and phylogenetic analyses were performed using clustalW, mega, the public core-genome MLST (cgMLST) scheme and an in-house bioinformatic single nucleotide polymorphism (SNP) typing pipeline. Results. Isolates of NTTB C. diphtheriae were recovered from four cases (cases 1 to 4) with epidermolysis bullosa attending the clinic. Two further isolates were subsequently recovered from case 4, >18 months later, and from two household contacts (cases 5 and 6) after a further 18 months and 3.5 years, respectively. All eight strains were NTTB C. diphtheriae biovar mitis, belonged to the same sequence type (ST-336) with the same deletion in tox. Phylogenetic analysis showed relatively high diversity between the eight strains with 7–199 SNP and 3–109 cgMLST loci differences between them. The number of SNPs between the three isolates from case 4 and two household contacts (cases 5 and 6) was 44–70 with 28–38 cgMLST loci differences. Conclusions. We report a cluster of NTTB C. diphtheriae cases in a skin clinic and evidence of onward household transmission. We conclude the deletion in the tox was responsible for the non-expression of DT. There was no evidence of reversion to DT expression over the 6.5 year period studied. These data informed revision to guidance in the management of NTTB cases and their contacts in the UK.

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“…Contributed to epidemiological studies of diphtheria in different regions of the world, from animal and human sources [85][86][87][88].…”

Section: Codes4strainsmentioning

confidence: 99%

Communicating and disseminating One Health: successes of the One Health European Joint Programme

Taylor,

Artursson,

Busani

et al. 2024

Journal of Medical Microbiology

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The application of a One Health approach recognizes that human health, animal health, plant health and ecosystem health are intrinsically connected. Tackling complex challenges associated with foodborne zoonoses, antimicrobial resistance, and emerging threats is imperative. Therefore, the One Health European Joint Programme was established within the European Union research programme Horizon 2020. The One Health European Joint Programme activities were based on the development and harmonization of a One Health science-based framework in the European Union (EU) and involved public health, animal health and food safety institutes from almost all EU Member States, the UK and Norway, thus strengthening the cooperation between public, medical and veterinary organizations in Europe. Activities including 24 joint research projects, 6 joint integrative projects and 17 PhD projects, and a multicountry simulation exercise facilitated harmonization of laboratory methods and surveillance, and improved tools for risk assessment. The provision of sustainable solutions is integral to a One Health approach. To ensure the legacy of the work of the One Health European Joint Programme, focus was on strategic communication and dissemination of the outputs and engagement of stakeholders at the national, European and international levels.

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A globalCorynebacterium diphtheriaegenomic framework sheds light on current diphtheria reemergence

Cited by 3 publications

References 74 publications

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

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

Household transmission of non-toxigenic diphtheria toxin gene-bearing Corynebacterium diphtheriae following a cluster of cutaneous cases in a specialist outpatient setting

Communicating and disseminating One Health: successes of the One Health European Joint Programme

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