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

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. [ABSTRACT FROM AUTHOR]