LGL, Bavarian Health and Food Safety Authority, Oberschleißheim, 85764 Germany.
LGL, Bavarian Health and Food Safety Authority, Oberschleißheim, 85764 Germany ; National Consiliary Laboratory on Diphtheria, Oberschleißheim, 85764 Germany.
Genome Med. 2014 Nov 28;6(11):113. doi: 10.1186/s13073-014-0113-3. eCollection 2014.
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.
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.
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.
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.
产毒溃疡棒状杆菌可引起类似白喉的人类疾病，已在家畜中发现，这些家畜被怀疑是人畜共患病传播的宿主。此外，产毒溃疡棒状杆菌近年来在许多工业化国家被报道在导致白喉方面发挥主导作用。
为了更深入地了解毒基因座，并详细了解传播途径，我们应用下一代测序和比较基因组学分析了来自人类患者及其家畜的 9 个分离株。
我们提供了产毒溃疡棒状杆菌人畜共传的分子证据，在 4 例中证明了下一代测序在流行病学研究中优于多位点序列分型的分辨率。此外，我们还提供了证据表明，通过获得新的毒力基因，溃疡棒状杆菌的毒力可以迅速发生变化。这一机制的一个例子是，一个分离株获得了一个在相应的家畜分离株中不存在的噬菌体。该噬菌体含有一个假定的新毒力因子，与沙门氏菌中的 RhuM 毒力因子高度同源，但在棒状杆菌中目前尚不清楚。此外，我们鉴定了一个携带白喉毒素基因的溃疡棒状杆菌的假定致病性岛。
新型假定的白喉毒素致病性岛可能通过水平基因转移为棒状杆菌提供了一种获得功能性白喉毒素编码基因的新途径和替代途径，与之前充分描述的噬菌体感染模型不同。新的传播途径可能解释了产毒溃疡棒状杆菌数量异常高的原因。
