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Interaction of Bartonella henselae with Fibronectin Represents the Molecular Basis for Adhesion to Host Cells

Vaca, Diana J ; Thibau, Arno ; Leisegang, Matthias S ; Malmström, Johan LU orcid ; Linke, Dirk ; Eble, Johannes A ; Ballhorn, Wibke ; Schaller, Martin ; Happonen, Lotta LU and Kempf, Volkhard A J (2022) In Microbiology spectrum 10(3).
Abstract

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... (More)

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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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bacterium-host interaction, Bartonella adhesin A, CRISPR-Cas, cross-linking mass spectrometry, extracellular matrix, trimeric autotransporter adhesin
in
Microbiology spectrum
volume
10
issue
3
article number
e0059822
publisher
American Society for Microbiology
external identifiers
  • scopus:85133214144
  • pmid:35435766
  • pmid:35435766
ISSN
2165-0497
DOI
10.1128/spectrum.00598-22
language
English
LU publication?
yes
id
0fd71c60-5843-41e0-92dd-883e6f9270a1
date added to LUP
2022-05-02 08:13:42
date last changed
2024-12-24 12:22:12
@article{0fd71c60-5843-41e0-92dd-883e6f9270a1,
  abstract     = {{<p>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.</p>}},
  author       = {{Vaca, Diana J and Thibau, Arno and Leisegang, Matthias S and Malmström, Johan and Linke, Dirk and Eble, Johannes A and Ballhorn, Wibke and Schaller, Martin and Happonen, Lotta and Kempf, Volkhard A J}},
  issn         = {{2165-0497}},
  keywords     = {{bacterium-host interaction; Bartonella adhesin A; CRISPR-Cas; cross-linking mass spectrometry; extracellular matrix; trimeric autotransporter adhesin}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{3}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Microbiology spectrum}},
  title        = {{Interaction of Bartonella henselae with Fibronectin Represents the Molecular Basis for Adhesion to Host Cells}},
  url          = {{http://dx.doi.org/10.1128/spectrum.00598-22}},
  doi          = {{10.1128/spectrum.00598-22}},
  volume       = {{10}},
  year         = {{2022}},
}