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Background <p><i>Corynebacterium diphtheriae</i>, the causative agent of diphtheria, remains a public health concern, especially in regions with low vaccination coverage. While advances in genomic typing, such as core-genome Multi-Locus Sequence Typing (cgMLST), have improved our ability for strain identification, a standardized and stable genomic taxonomy is still lacking. This study aimed to establish a consistent taxonomic classification and nomenclature for <i>C. diphtheriae</i> strains using cgMLST-based Life Identification Number (LIN) codes.</p> Methods <p>Comparing 1,665 genomes from <i>C. diphtheriae</i> and closely related species <i>C. belfantii</i> and <i>C. rouxii</i>, we observed population-level genetic discontinuities in cgMLST profiles dissimilarities, and established hierarchical taxonomic levels based on optimal allelic difference thresholds. Ten-level LIN codes were defined, encompassing broad population structure subdivisions and fine-scale epidemiological levels. The LIN code system was implemented into the BIGSdb-Pasteur platform, and nicknames derived from the 7-loci MLST sequence types were given to sublineages and clonal groups.</p> Results <p>cgMLST genetic thresholds were first defined at species and lineage levels (minimum of 1,240 and 1,035 allelic differences, respectively). Sublineages (SL), clonal groups (ClG), and genetic clusters (GC) were next defined with progressively finer allelic mismatch thresholds (500, 55, and 25 differences, respectively). A broad population diversity of <i>C. diphtheriae</i> was uncovered, with the distinction of &gt; 400 SLs and &gt; 1,000 GCs. For epidemiological purposes, five shallow-level thresholds (8, 4, 2,1, and 0 allelic mismatches) were defined, completing the 10-level LIN code taxonomy. We illustrate LIN codes applicability to investigate the genetic diversity and transmission chains of relevant clusters, such as SL8 (the 1990s ex-USSR outbreak) or SL384 (involved in outbreaks in Yemen and Europe).</p> Conclusions <p>The cgMLST-based LIN code system provides a stable genomic taxonomy for strains of <i>C. diphtheriae, C. rouxii</i> and <i>C. belfantii</i>. By defining ten hierarchical levels of resolution, this system effectively captures its phylogenetic diversity, facilitating population biology research and epidemiological surveillance. The public availability of this system in the BIGSdb-Pasteur platform provides a standardized framework for diphtheria genomic epidemiology with potential to harmonize global surveillance of diphtheria resurgence.</p>

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Life Identification Number (LIN) codes for the genomic taxonomy of Corynebacterium diphtheriae strains

  • 期刊论文

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  • 发表日期：

    2025年12月6日

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  • Jose F. Delgado-Blas,
  • Martin Rethoret-Pasty,
  • Sylvain Brisse

摘要

Background

Corynebacterium diphtheriae, the causative agent of diphtheria, remains a public health concern, especially in regions with low vaccination coverage. While advances in genomic typing, such as core-genome Multi-Locus Sequence Typing (cgMLST), have improved our ability for strain identification, a standardized and stable genomic taxonomy is still lacking. This study aimed to establish a consistent taxonomic classification and nomenclature for C. diphtheriae strains using cgMLST-based Life Identification Number (LIN) codes.

Methods

Comparing 1,665 genomes from C. diphtheriae and closely related species C. belfantii and C. rouxii, we observed population-level genetic discontinuities in cgMLST profiles dissimilarities, and established hierarchical taxonomic levels based on optimal allelic difference thresholds. Ten-level LIN codes were defined, encompassing broad population structure subdivisions and fine-scale epidemiological levels. The LIN code system was implemented into the BIGSdb-Pasteur platform, and nicknames derived from the 7-loci MLST sequence types were given to sublineages and clonal groups.

Results

cgMLST genetic thresholds were first defined at species and lineage levels (minimum of 1,240 and 1,035 allelic differences, respectively). Sublineages (SL), clonal groups (ClG), and genetic clusters (GC) were next defined with progressively finer allelic mismatch thresholds (500, 55, and 25 differences, respectively). A broad population diversity of C. diphtheriae was uncovered, with the distinction of > 400 SLs and > 1,000 GCs. For epidemiological purposes, five shallow-level thresholds (8, 4, 2,1, and 0 allelic mismatches) were defined, completing the 10-level LIN code taxonomy. We illustrate LIN codes applicability to investigate the genetic diversity and transmission chains of relevant clusters, such as SL8 (the 1990s ex-USSR outbreak) or SL384 (involved in outbreaks in Yemen and Europe).

Conclusions

The cgMLST-based LIN code system provides a stable genomic taxonomy for strains of C. diphtheriae, C. rouxii and C. belfantii. By defining ten hierarchical levels of resolution, this system effectively captures its phylogenetic diversity, facilitating population biology research and epidemiological surveillance. The public availability of this system in the BIGSdb-Pasteur platform provides a standardized framework for diphtheria genomic epidemiology with potential to harmonize global surveillance of diphtheria resurgence.