Corynebacterium diphtheriae: genome diversity, population structure and genotyping perspectives.

The epidemic re-emergence of diphtheria in Russia and the Newly Independent States (NIS) of the former Soviet Union in the 1990s demonstrated the continued threat of this thought to be rare disease. The bacteriophage encoded toxin is a main virulence factor of Corynebacterium diphtheriae, however, an analysis of the first complete genome sequence of C. diphtheriae revealed a recent acquisition of other pathogenicity factors including iron-uptake systems, adhesins and fimbrial proteins as indeed this extracellular pathogen has more possibilities for lateral gene transfer than, e.g., its close relative, mainly intracellular Mycobacterium tuberculosis. C. diphtheriae appears to have a phylogeographical structure mainly represented by area-specific variants whose circulation is under strong influence of human host factors, including health control measures, first of all, vaccination, and social economic conditions. This framework core population structure may be challenged by importation of the endemic and eventually toxigenic strains from new areas thus leading to localized or large epidemics caused directly by imported strains or by bacteriophage-lysogenized indigenous strains converted into toxin production. A feature of C. diphtheriae co-existence with humans is its periodicity: following large epidemic in the 1990s, the present period is marked by increasing heterogeneity of the circulating populations whereas re-emergence of new toxigenic variants along with persistent circulation of invasive non-toxigenic strains appear alarming. To identify and rapidly monitor subtle changes in the genome structure at an infraclonal level during and between epidemics, portable and discriminatory typing methods of C. diphtheriae are still needed. In this view, CRISPRs and minisatellites are promising genomic markers for development of high-resolution typing schemes and databasing of C. diphtheriae.