Abstract
BackgroundToxigenic 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.MethodsTo 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.ResultsWe 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.ConclusionThe 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 materialThe online version of this article (doi:10.1186/s13073-014-0113-3) contains supplementary material, which is available to authorized users.
Highlights
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
We wondered whether this phenomenon could be due to a higher proportion of toxigenic versus non-toxigenic C. ulcerans compared with the proportion of toxigenic versus non-toxigenic C. diphtheriae
The isolates analyzed here were sent for differentiation to the National Consiliary Laboratory on Diphtheria (NCLoD) by several clinical microbiology laboratories and as a caveat might not be representative of the whole Corynebacterium population in Germany and several of the Corynebacteria were isolated from animals
Summary
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. DT is a very potent toxin that is able to act on many different types of cells (reviewed in [16]). This Y-shaped protein toxin was shown by X-ray crystallography to consist of three domains [17]. The translocator domain forms the middle part of the toxin and is able to integrate into the endosomal membrane upon the pH change after endocytosis, thereby transferring the amino-terminal, catalytically active part of the toxin into the cytoplasm. Even a single DT molecule is sufficient to kill a eukaryotic cell [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
