Insights into old and new foes: Pan-genomics of Corynebacterium diphtheriae and Corynebacterium ulcerans

Diphtheria, a toxin-mediated disease of upper respiratory tract in humans caused by Corynebacterium diphtheriae, has been a global healthcare challenge responsible for a significant mortality in the pre-vaccination era and more recently, in the regions with poor immunization coverage. Historically, biochemical characteristics are used for subdividing C. diphtheriae strains into four biovars, that is, mitis, gravis, intermedius, and belfanti. However, this differentiation is not useful in tracing the pathogen transmission and characterizing outbreak-associated strains. Genetic approaches, for example, multilocus sequence typing (MLST) and ribotyping have been developed and used for evolutionary and epidemiological characterization until the introduction of next-generation sequencing. Pan-genomic approaches improved our understanding of evolutionary dynamics and virulence characteristics of C. diphtheriae strains, particularly in respect to the genetic factors associated with invasive infections caused by nontoxigenic strains. Corynebacterium ulcerans, a close relative of C. diphtheriae, has recently emerged as an important zoonotic pathogen that also causes diphtheria-like infections in humans. Genome-based studies also provided important knowledge of the major lineages and virulence potential of C. ulcerans.