Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A
ABSTRACT Adhesion to host cells is the first and most crucial step in infections with pathogenic Gram-negative bacteria and is often mediated by trimeric autotransporter adhesins (TAAs). Bartonella henselae targets the extracellular matrix glycoprotein fibronectin (Fn) via the Bartonella adhesin A (...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02117-22 |
| _version_ | 1811329723301625856 |
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| author | Arno Thibau Diana J. Vaca Marlene Bagowski Katharina Hipp Daniela Bender Wibke Ballhorn Dirk Linke Volkhard A. J. Kempf |
| author_facet | Arno Thibau Diana J. Vaca Marlene Bagowski Katharina Hipp Daniela Bender Wibke Ballhorn Dirk Linke Volkhard A. J. Kempf |
| author_sort | Arno Thibau |
| collection | DOAJ |
| description | ABSTRACT Adhesion to host cells is the first and most crucial step in infections with pathogenic Gram-negative bacteria and is often mediated by trimeric autotransporter adhesins (TAAs). Bartonella henselae targets the extracellular matrix glycoprotein fibronectin (Fn) via the Bartonella adhesin A (BadA) attaching the bacteria to the host cell. The TAA BadA is characterized by a highly repetitive passenger domain consisting of 30 neck/stalk domains with various degrees of similarity. To elucidate the motif sequences mediating Fn binding, we generated 10 modified BadA constructs and verified their expression via Western blotting, confocal laser scanning, and electron microscopy. We analyzed their ability to bind human plasma Fn using quantitative whole-cell enzyme-linked immunosorbent assays (ELISAs) and fluorescence microscopy. Polyclonal antibodies targeting a 15-mer amino acid motif sequence proved to reduce Fn binding. We suggest that BadA adheres to Fn in a cumulative effort with quick saturation primarily via unpaired β-strands appearing in motifs repeatedly present throughout the neck/stalk region. In addition, we demonstrated that the length of truncated BadA constructs correlates with the immunoreactivity of human patient sera. The identification of BadA-Fn binding regions will support the development of new “antiadhesive” compounds inhibiting the initial adherence of B. henselae and other TAA-expressing pathogens to host cells. IMPORTANCE Trimeric autotransporter adhesins (TAAs) are important virulence factors and are widely present in various pathogenic Gram-negative bacteria. TAA-expressing bacteria cause a wide spectrum of human diseases, such as cat scratch disease (Bartonella henselae), enterocolitis (Yersinia enterocolitica), meningitis (Neisseria meningitis), and bloodstream infections (multidrug-resistant Acinetobacter baumannii). TAA-targeted antiadhesive strategies (against, e.g., Bartonella adhesin A [BadA], Yersinia adhesin A [YadA], Neisseria adhesin A [NadA], and Acinetobacter trimeric autotransporter [Ata]) might represent a universal strategy to counteract such bacterial infections. BadA is one of the best characterized TAAs, and because of its high number of (sub)domains, it serves as an attractive adhesin to study the domain-function relationship of TAAs in the infection process. The identification of common binding motifs between TAAs (here, BadA) and their major binding partner (here, fibronectin) provides a basis toward the design of novel “antiadhesive” compounds preventing the initial adherence of Gram-negative bacteria in infections. |
| first_indexed | 2024-04-13T15:48:56Z |
| format | Article |
| id | doaj.art-b0a5878974c14e8998a96c813be5ae65 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T15:48:56Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-b0a5878974c14e8998a96c813be5ae652022-12-22T02:40:54ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.02117-22Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin AArno Thibau0Diana J. Vaca1Marlene Bagowski2Katharina Hipp3Daniela Bender4Wibke Ballhorn5Dirk Linke6Volkhard A. J. Kempf7Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, GermanyInstitute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, GermanyInstitute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, GermanyElectron Microscopy Facility, Max Planck Institute for Developmental Biology, Tübingen, GermanyFederal Institute for Vaccines and Biomedicines, Department of Virology, Paul-Ehrlich-Institut, Langen, GermanyInstitute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, GermanySection for Genetics and Evolutionary Biology, Department of Biosciences, University of Oslo, Oslo, NorwayInstitute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, GermanyABSTRACT Adhesion to host cells is the first and most crucial step in infections with pathogenic Gram-negative bacteria and is often mediated by trimeric autotransporter adhesins (TAAs). Bartonella henselae targets the extracellular matrix glycoprotein fibronectin (Fn) via the Bartonella adhesin A (BadA) attaching the bacteria to the host cell. The TAA BadA is characterized by a highly repetitive passenger domain consisting of 30 neck/stalk domains with various degrees of similarity. To elucidate the motif sequences mediating Fn binding, we generated 10 modified BadA constructs and verified their expression via Western blotting, confocal laser scanning, and electron microscopy. We analyzed their ability to bind human plasma Fn using quantitative whole-cell enzyme-linked immunosorbent assays (ELISAs) and fluorescence microscopy. Polyclonal antibodies targeting a 15-mer amino acid motif sequence proved to reduce Fn binding. We suggest that BadA adheres to Fn in a cumulative effort with quick saturation primarily via unpaired β-strands appearing in motifs repeatedly present throughout the neck/stalk region. In addition, we demonstrated that the length of truncated BadA constructs correlates with the immunoreactivity of human patient sera. The identification of BadA-Fn binding regions will support the development of new “antiadhesive” compounds inhibiting the initial adherence of B. henselae and other TAA-expressing pathogens to host cells. IMPORTANCE Trimeric autotransporter adhesins (TAAs) are important virulence factors and are widely present in various pathogenic Gram-negative bacteria. TAA-expressing bacteria cause a wide spectrum of human diseases, such as cat scratch disease (Bartonella henselae), enterocolitis (Yersinia enterocolitica), meningitis (Neisseria meningitis), and bloodstream infections (multidrug-resistant Acinetobacter baumannii). TAA-targeted antiadhesive strategies (against, e.g., Bartonella adhesin A [BadA], Yersinia adhesin A [YadA], Neisseria adhesin A [NadA], and Acinetobacter trimeric autotransporter [Ata]) might represent a universal strategy to counteract such bacterial infections. BadA is one of the best characterized TAAs, and because of its high number of (sub)domains, it serves as an attractive adhesin to study the domain-function relationship of TAAs in the infection process. The identification of common binding motifs between TAAs (here, BadA) and their major binding partner (here, fibronectin) provides a basis toward the design of novel “antiadhesive” compounds preventing the initial adherence of Gram-negative bacteria in infections.https://journals.asm.org/doi/10.1128/spectrum.02117-22Bartonella adhesin Atrimeric autotransporter adhesinfibronectinpathogenicitybacterium-host interaction |
| spellingShingle | Arno Thibau Diana J. Vaca Marlene Bagowski Katharina Hipp Daniela Bender Wibke Ballhorn Dirk Linke Volkhard A. J. Kempf Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A Microbiology Spectrum Bartonella adhesin A trimeric autotransporter adhesin fibronectin pathogenicity bacterium-host interaction |
| title | Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A |
| title_full | Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A |
| title_fullStr | Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A |
| title_full_unstemmed | Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A |
| title_short | Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of Bartonella Adhesin A |
| title_sort | adhesion of bartonella henselae to fibronectin is mediated via repetitive motifs present in the stalk of bartonella adhesin a |
| topic | Bartonella adhesin A trimeric autotransporter adhesin fibronectin pathogenicity bacterium-host interaction |
| url | https://journals.asm.org/doi/10.1128/spectrum.02117-22 |
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