Phylogenomic diversity within Corynebacterium diphtheriae, a reemerging threat to global public health

Diphtheria is caused by toxin-producing strains of Corynebacterium diphtheriae that colonize the upper respiratory tract in humans. Nontoxigenic C. diphtheriae strains are also causing severe invasive infections resulting in significant mortality, which is exacerbated by emerging multidrug resistance. Multiple antimicrobial resistance genes such as ermX can be plasmid-borne or are carried by integrons such as dfrA16 and sul1 that are easily transferable between C. diphtheriae strains via homologous recombination and horizontal gene transfer. Phylogenomically, C. diphtheriae is highly diverse with global cocirculation of multiple toxigenic and nontoxigenic lineages. The current toxoid vaccine is highly effective, but more efforts are needed to ensure global compliance and to conduct immunization programs, especially among migrants. Several moderate to high-impact mutations with the potential to introduce structural changes to the toxin have been observed in the tox gene. These mutations need further investigations to test the efficacy of a current vaccine against them.