Antunes Camila Azevedo, Sanches dos Santos Louisy, Hacker Elena, Köhler Stefanie, Bösl Korbinian, Ott Lisa, de Luna Maria das Graças, Hirata Raphael, Azevedo Vasco Ariston de Carvalho, Mattos-Guaraldi Ana-Luíza, Burkovski Andreas
Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Departmento de Biologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Microbiology (Reading). 2015 Mar;161(Pt 3):639-47. doi: 10.1099/mic.0.000020. Epub 2015 Jan 29.
Corynebacterium diphtheriae is typically recognized as an extracellular pathogen. However, a number of studies revealed its ability to invade epithelial cells, indicating a more complex pathogen-host interaction. The molecular mechanisms controlling and facilitating internalization of Cor. diphtheriae are poorly understood. In this study, we investigated the role of DIP0733 as virulence factor to elucidate how it contributes to the process of pathogen-host cell interaction. Based on in vitro experiments, it was suggested recently that the DIP0733 protein might be involved in adhesion, invasion of epithelial cells and induction of apoptosis. A corresponding Cor. diphtheriae mutant strain generated in this study was attenuated in its ability to colonize and kill the host in a Caenorhabditis elegans infection model system. Furthermore, the mutant showed an altered adhesion pattern and a drastically reduced ability to adhere and invade epithelial cells. Subsequent experiments showed an influence of DIP0733 on binding of Cor. diphtheriae to extracellular matrix proteins such as collagen and fibronectin. Furthermore, based on its fibrinogen-binding activity, DIP0733 may play a role in avoiding recognition of Cor. diphtheriae by the immune system. In summary, our findings support the idea that DIP0733 is a multi-functional virulence factor of Cor. diphtheriae.
白喉棒状杆菌通常被认为是一种胞外病原体。然而，多项研究揭示了其侵入上皮细胞的能力，这表明病原体与宿主之间的相互作用更为复杂。目前对白喉棒状杆菌内化过程的控制和促进分子机制了解甚少。在本研究中，我们研究了DIP0733作为毒力因子的作用，以阐明它如何促进病原体与宿主细胞的相互作用过程。基于体外实验，最近有研究表明DIP0733蛋白可能参与上皮细胞的黏附、侵袭及凋亡诱导。本研究构建的相应白喉棒状杆菌突变株在秀丽隐杆线虫感染模型系统中定殖和杀死宿主的能力减弱。此外，该突变株表现出黏附模式改变，黏附和侵袭上皮细胞的能力大幅降低。后续实验表明DIP0733对白喉棒状杆菌与细胞外基质蛋白（如胶原蛋白和纤连蛋白）的结合有影响。此外，基于其纤维蛋白原结合活性，DIP0733可能在逃避免疫系统对白喉棒状杆菌的识别中发挥作用。总之，我们的研究结果支持DIP0733是白喉棒状杆菌多功能毒力因子这一观点。
