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Background  Toxigenic  Corynebacterium ulcerans  can cause a diphtheria-like illness in humans and have been found in domestic animals, which were suspected to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic  C. ulcerans  were reported to take over the leading role in causing diphtheria in the last years in many industrialized countries.    Methods  To gain deeper insights into the  tox  gene locus and to understand the transmission pathway in detail, we analyzed nine isolates derived from human patients and their domestic animals applying next generation sequencing and comparative genomics.    Results  We provide molecular evidence for zoonotic transmission of  C. ulcerans  in four cases and demonstrate the superior resolution of next generation sequencing compared to multi-locus sequence typing for epidemiologic research. Additionally, we provide evidence that the virulence of  C. ulcerans  can change rapidly by acquisition of novel virulence genes. This mechanism is exemplified by an isolate which acquired a prophage not present in the corresponding isolate from the domestic animal. This prophage contains a putative novel virulence factor, which shares high identity with the RhuM virulence factor from  Salmonella enterica  but which is unknown in Corynebacteria so far. Furthermore, we identified a putative pathogenicity island for  C. ulcerans  bearing a diphtheria toxin gene.    Conclusion  The novel putative diphtheria toxin pathogenicity island could provide a new and alternative pathway for Corynebacteria to acquire a functional diphtheria toxin-encoding gene by horizontal gene transfer, distinct from the previously well characterized phage infection model. The novel transmission pathway might explain the unexpectedly high number of toxigenic  C. ulcerans.Electronic supplementary material  The online version of this article (doi:10.1186/s13073-014-0113-3) contains supplementary material, which is available to authorized users.

genome medicine

Next generation sequencing analysis of nine Corynebacterium ulcerans isolates reveals zoonotic transmission and a novel putative diphtheria toxin-encoding pathogenicity island