Weidensdorfer Marko, Chae Ju Ik, Makobe Celestine, Stahl Julia, Averhoff Beate, Müller Volker, Schürmann Christoph, Brandes Ralf P, Wilharm Gottfried, Ballhorn Wibke, Christ Sara, Linke Dirk, Fischer Doris, Göttig Stephan, Kempf Volkhard A J
University Hospital, Goethe-University, Institute for Medical Microbiology and Infection Control, Frankfurt am Main, Germany.
Department of Molecular Microbiology and Bioenergetics, Institute of Molecular Biosciences, Goethe-University, Frankfurt am Main, Germany.
Infect Immun. 2015 Dec 28;84(3):711-22. doi: 10.1128/IAI.01502-15.
Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples ("organ microbiology") might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially.
细菌黏附决定了许多人类致病细菌的毒力。主要使用细胞微生物学方法对这一早期感染事件进行了更详细阐释的实验研究。然而，细胞单层的体外感染仅部分反映了体内情况，并且许多人类致病细菌没有可用的动物感染模型。因此，人器官的离体感染可能是克服这些局限性的一种有吸引力的方法。我们在模拟人类内皮细胞体内感染情况的动态流动条件下，将汉赛巴尔通体或鲍曼不动杆菌离体感染整个人类脐带。为此，建立了定量内皮细胞黏附的野生型和三聚体自转运黏附素（TAA）缺陷型细菌的方法。数据显示：（i）鲍曼不动杆菌以TAA依赖的方式与内皮细胞结合；（ii）这种器官感染模型导致高度可重复的黏附率；此外，（iii）该模型能够剖析TAA在人类感染自然过程中的生物学功能。这些发现表明，使用离体人类组织样本的感染模型（“器官微生物学”）可能是分析细菌致病性的有价值工具，至少部分能够替代动物感染模型。
