Identification of a diphtheria toxin-like gene family beyond the Corynebacterium genus

FEBS Lett. 2018 Aug;592(16):2693-2705. doi: 10.1002/1873-3468.13208. Epub 2018 Aug 16.


Diphtheria toxin (DT), produced by Corynebacterium diphtheria, is the causative agent of diphtheria and one of the most potent protein toxins known; however, it has an unclear evolutionary history. Here, we report the discovery of a DT-like gene family in several bacterial lineages outside of Corynebacterium, including Austwickia and Streptomyces. These DT-like genes form sister lineages in the DT phylogeny and conserve key DT features including catalytic and translocation motifs, but possess divergent receptor-binding domains. DT-like genes are not associated with corynephage, but have undergone lateral transfer through a separate mechanism. The discovery of the first non-Corynebacterium homologs of DT sheds light on its evolutionary origin and highlights novelties that may have resulted in the emergence of DT targeting humans.

Keywords: Austwickia; Streptomyces; ADP-ribosylating toxins; Actinobacteria; diphtheria toxin; evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / genetics
  • Actinobacteria / metabolism
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Catalytic Domain
  • Cloning, Molecular
  • Corynebacterium / genetics
  • Corynebacterium / metabolism
  • Diphtheria Toxin / genetics
  • Evolution, Molecular
  • Gene Transfer, Horizontal
  • Models, Molecular
  • Multigene Family
  • Phylogeny
  • Protein Conformation
  • Streptomyces / genetics
  • Streptomyces / metabolism*


  • Bacterial Toxins
  • Diphtheria Toxin

Associated data

  • GENBANK/WP_040322835.1
  • GENBANK/AAN28948.1
  • GENBANK/WP_014654963.1
  • GENBANK/WP_073156187.1
  • GENBANK/WP_078659863.1
  • GENBANK/PSJ28985.1
  • GENBANK/WP_079110321.1
  • GENBANK/SDT83331.1
  • GENBANK/WP_093864399.1
  • GENBANK/WP_095582082.1