Dataset Information

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model.

ABSTRACT: 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.

SUBMITTER: Weidensdorfer M

PROVIDER: S-EPMC4771361 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model.

Weidensdorfer Marko M Chae Ju Ik JI Makobe Celestine C Stahl Julia J Averhoff Beate B Müller Volker V Schürmann Christoph C Brandes Ralf P RP Wilharm Gottfried G Ballhorn Wibke W Christ Sara S Linke Dirk D Fischer Doris D Göttig Stephan S Kempf Volkhard A J VA

Infection and immunity 20151228 3

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 th ...[more]

PMID: 26712205

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Project description:Acinetobacter baumannii is an antibiotic-resistant, Gram-negative pathogen that causes a multitude of nosocomial infections. However, pathogenicity mechanisms and the host cell response during infection remain unclear. In this study, we determined virulence traits of A. baumannii clinical isolates belonging to the most widely disseminated international clonal lineage, international cluster 2 (IC2), in vitro and in vivo. Complexome profiling of primary human endothelial cells with A. baumannii revealed that mitochondria, and in particular complexes of the electron transport chain, are important host cell targets. Infection with highly virulent A. baumannii remodelled assembly of mitochondrial protein complexes and led to metabolic adaptation. These were characterized by reduced mitochondrial respiration and glycolysis in contrast to those observed in infection with low-pathogenicity A. baumannii. Perturbation of oxidative phosphorylation, destabilization of mitochondrial ribosomes, and interference with mitochondrial metabolic pathways were identified as important pathogenicity mechanisms. Understanding the interaction of human host cells with the current global A. baumannii clone is the basis to identify novel therapeutic targets. IMPORTANCE Virulence traits of Acinetobacter baumannii isolates of the worldwide most prevalent international clonal lineage, IC2, remain largely unknown. In our study, multidrug-resistant IC2 clinical isolates differed substantially in their virulence potential despite their close genetic relatedness. Our data suggest that, at least for some isolates, mitochondria are important target organelles during infection of primary human endothelial cells. Complexes of the respiratory chain were extensively remodelled after infection with a highly virulent A. baumannii strain, leading to metabolic adaptation characterized by severely reduced respiration and glycolysis. Perturbations of both mitochondrial morphology and mitoribosomes were identified as important pathogenicity mechanisms. Our data might help to further decipher the molecular mechanisms of A. baumannii and host mitochondrial interaction during infection.

Dataset Information

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model.

Publications

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model.

Similar Datasets

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