Genome-wide comparison of toxigenic and non-toxigenicCorynebacterium diphtheriaeisolates identifies differences in the pan genomes between respiratory and cutaneous strains

Abstract

AbstractObjectivesCorynebacterium diphtheriaeis the main etiological agent of diphtheria, a global disease causing life-threatening infections, particularly in infants and children. Vaccination with diphtheria toxoid protects against infection with potent toxin producing strains. However a growing number of apparently non-toxigenic but potentially invasiveC. diphtheriaestrains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species.MethodsThis study examined genomic diversity among 47C. diphtheriaeisolates collected in Australia over a 10-year period using whole genome sequencing. Phylogeny was determined using SNP-based mapping and genome wide analysis.ResultsC. diphtheriaesequence type (ST) 32, a non-toxigenic ST with evidence of enhanced virulence that is also circulating in Europe, appears to be endemic in Australia. Isolates from temporospatially related patients displayed the same ST and similarity in their core genomes. The genome-wide analysis highlighted a role of pilins, adhesion factors and iron utilization in infections caused by toxigenic as well as non-toxigenic strains.ConclusionsThe genomic diversity of toxigenic and non-toxigenic strains ofC. diphtheriaein Australia suggests multiple local and overseas sources of infection and colonisation. Our findings suggest that regular genomic surveillance of co-circulating toxigenic and non-toxigenicC. diphtheriaecan deliver highly nuanced data in order to inform targeted public health actions and policy for predicting the future impact of this highly successful pathogen.