Interaction of Bartonella henselae with fibronectin represents the molecular basis for adhesion to host cells

  • Bacterial adhesion to the host is the most decisive step in infections. Trimeric autotransporter adhesins (TAA) are important pathogenicity factors of Gram-negative bacteria. The prototypic TAA Bartonella adhesin A (BadA) from human-pathogenic Bartonella henselae mediates bacterial adherence to endothelial cells (ECs) and extracellular matrix proteins. Here, we determined the interaction between BadA and fibronectin (Fn) to be essential for bacterial host cell adhesion. BadA interactions occur within the heparin-binding domains of Fn. The exact binding sites were revealed by mass spectrometry analysis of chemically cross-linked whole-cell bacteria and Fn. Specific BadA interactions with defined Fn regions represent the molecular basis for bacterial adhesion to ECs and these data were confirmed by BadA-deficient bacteria and CRISPR-Cas knockout Fn host cells. Interactions between TAAs and the extracellular matrix might represent the key step for adherence of human-pathogenic Gram-negative bacteria to the host. IMPORTANCE Deciphering the mechanisms of bacterial host cell adhesion is a clue for preventing infections. We describe the underestimated role that the extracellular matrix protein fibronectin plays in the adhesion of human-pathogenic Bartonella henselae to host cells. Fibronectin-binding is mediated by a trimeric autotransporter adhesin (TAA) also present in many other human-pathogenic Gram-negative bacteria. We demonstrate that both TAA and host-fibronectin contribute significantly to bacterial adhesion, and we present the exact sequence of interacting amino acids from both proteins. Our work shows the domain-specific pattern of interaction between the TAA and fibronectin to adhere to host cells and opens the perspective to fight bacterial infections by inhibiting bacterial adhesion which represents generally the first step in infections.

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Metadaten
Author:Diana Jaqueline Vaca LlerenaORCiDGND, Arno ThibauGND, Matthias LeisegangORCiDGND, Johan MalmströmORCiD, Dirk LinkeORCiD, Johannes A. EbleORCiDGND, Wibke Ballhorn, Martin SchallerGND, Lotta HapponenORCiD, Volkhard A. J. KempfORCiDGND
URN:urn:nbn:de:hebis:30:3-819490
DOI:https://doi.org/10.1128/spectrum.00598-22
Parent Title (English):Microbiology spectrum
Publisher:American Society for Microbiology
Place of publication:Birmingham, Ala.
Document Type:Article
Language:English
Date of Publication (online):2022/04/18
Date of first Publication:2022/04/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/03/14
Volume:10
Issue:3, e00598
Article Number:e00598
Page Number:15
HeBIS-PPN:519460405
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International