Evidence of episodic positive selection in Corynebacterium diphtheriae complex of species and its implementations in identification of drug and vaccine targets

PeerJ. 2022 Feb 16:10:e12662. doi: 10.7717/peerj.12662. eCollection 2022.


Background: Within the pathogenic bacterial species Corynebacterium genus, six species that can produce diphtheria toxin (C. belfantii, C. diphtheriae, C. pseudotuberculosis, C. rouxii, C. silvaticum and C. ulcerans) form a clade referred to as the C. diphtheria complex. These species have been found in humans and other animals, causing diphtheria or other diseases. Here we show the results of a genome scale analysis to identify positive selection in protein-coding genes that may have resulted in the adaptations of these species to their ecological niches and suggest drug and vaccine targets.

Methods: Forty genomes were sampled to represent species, subspecies or biovars of Corynebacterium. Ten phylogenetic groups were tested for positive selection using the PosiGene pipeline, including species and biovars from the C. diphtheria complex. The detected genes were tested for recombination and had their sequences alignments and homology manually examined. The final genes were investigated for their function and a probable role as vaccine or drug targets.

Results: Nineteen genes were detected in the species C. diphtheriae (two), C. pseudotuberculosis (10), C. rouxii (one), and C. ulcerans (six). Those were found to be involved in defense, translation, energy production, and transport and in the metabolism of carbohydrates, amino acids, nucleotides, and coenzymes. Fourteen were identified as essential genes, and six as virulence factors. Thirteen from the 19 genes were identified as potential drug targets and four as potential vaccine candidates. These genes could be important in the prevention and treatment of the diseases caused by these bacteria.

Keywords: Corynebacterium; Drug target; Positive selection; Vaccine target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corynebacterium
  • Corynebacterium diphtheriae* / genetics
  • Diphtheria* / prevention & control
  • Humans
  • Phylogeny
  • Vaccines*


  • Vaccines

Grants and funding

This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.