A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae

PLoS Genet. 2023 Apr 26;19(4):e1010737. doi: 10.1371/journal.pgen.1010737. eCollection 2023 Apr.


Diphtheria is a respiratory disease caused by Corynebacterium diphtheriae. While the toxin-based vaccine has helped control outbreaks of the disease since the mid-20th century there has been an increase in cases in recent years, including systemic infections caused by non-toxigenic C. diphtheriae strains. Here we describe the first study of gene essentiality in C. diphtheriae, providing the most-dense Transposon Directed Insertion Sequencing (TraDIS) library in the phylum Actinobacteriota. This high-density library has allowed the identification of conserved genes across the genus and phylum with essential function and enabled the elucidation of essential domains within the resulting proteins including those involved in cell envelope biogenesis. Validation of these data through protein mass spectrometry identified hypothetical and uncharacterized proteins in the proteome which are also represented in the vaccine. These data are an important benchmark and useful resource for the Corynebacterium, Mycobacterium, Nocardia and Rhodococcus research community. It enables the identification of novel antimicrobial and vaccine targets and provides a basis for future studies of Actinobacterial biology.

MeSH terms

  • Corynebacterium diphtheriae* / genetics
  • Diphtheria* / epidemiology
  • Diphtheria* / microbiology
  • Disease Outbreaks
  • Gene Library
  • Humans
  • Multiomics

Grants and funding

PAH would also like to acknowledge funding from Medical Research Scotland (422 FRG) and the Royal Academy of Engineering Research Chair Scheme for long-term personal research support (RCSRF2021\11\15); PAH received a salary from RAEng for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.