Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University Frankfurt am Main, Paul-Ehrlich-Str. 40, 60596, Frankfurt, Germany.
Institute for Medical Microbiology and Infection Control, University Hospital, Eberhard Karls-University, Tübingen, Germany.
Med Microbiol Immunol. 2020 Jun;209(3):277-299. doi: 10.1007/s00430-019-00644-3. Epub 2019 Nov 29.
The capacity of pathogenic microorganisms to adhere to host cells and avoid clearance by the host immune system is the initial and most decisive step leading to infections. Bacteria have developed different strategies to attach to diverse host surface structures. One important strategy is the adhesion to extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, laminin) that are highly abundant in connective tissue and basement membranes. Gram-negative bacteria express variable outer membrane proteins (adhesins) to attach to the host and to initiate the process of infection. Understanding the underlying molecular mechanisms of bacterial adhesion is a prerequisite for targeting this interaction by "anti-ligands" to prevent colonization or infection of the host. Future development of such "anti-ligands" (specifically interfering with bacteria-host matrix interactions) might result in the development of a new class of anti-infective drugs for the therapy of infections caused by multidrug-resistant Gram-negative bacteria. This review summarizes our current knowledge about the manifold interactions of adhesins expressed by Gram-negative bacteria with ECM proteins and the use of this information for the generation of novel therapeutic antivirulence strategies.
病原体微生物黏附宿主细胞并逃避宿主免疫系统清除的能力是导致感染的初始和最决定性步骤。细菌已经发展出不同的策略来附着于不同的宿主表面结构。一种重要的策略是黏附于细胞外基质 (ECM) 蛋白(例如胶原、纤维连接蛋白、层粘连蛋白),这些蛋白在结缔组织和基底膜中含量丰富。革兰氏阴性菌表达可变的外膜蛋白(黏附素)来附着于宿主并启动感染过程。了解细菌黏附的潜在分子机制是通过“抗配体”靶向这种相互作用以防止宿主定植或感染的前提。此类“抗配体”(专门干扰细菌-宿主基质相互作用)的未来发展可能会导致开发一类新的抗传染性药物,用于治疗由耐多药革兰氏阴性菌引起的感染。这篇综述总结了我们目前对革兰氏阴性菌表达的黏附素与 ECM 蛋白的多种相互作用的认识,并利用这些信息来产生新的治疗抗病毒策略。