Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A
ABSTRACT The fibronectin-binding protein A (FnBPA) is a cell surface-associated protein of Staphylococcus aureus which mediates adherence to the host extracellular matrix and is important for bacterial virulence. Previously, substantial sequence diversity was found among strains in the fibrinogen-bi...
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American Society for Microbiology
2018
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oai:doaj.org-article:da1ec3d8e8bb47a68f575bab5078855f2021-11-15T15:22:14ZHuman Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A10.1128/mSphere.00590-172379-5042https://doaj.org/article/da1ec3d8e8bb47a68f575bab5078855f2018-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00590-17https://doaj.org/toc/2379-5042ABSTRACT The fibronectin-binding protein A (FnBPA) is a cell surface-associated protein of Staphylococcus aureus which mediates adherence to the host extracellular matrix and is important for bacterial virulence. Previously, substantial sequence diversity was found among strains in the fibrinogen-binding A domain of this protein, and 7 different isotypes were described. The effect of this sequence diversity on the human antibody response, in terms of both antibody production and antibody function, remains unclear. In this study, we identify five different FnBPA A domain isotypes based on the sequence results of 22 clinical S. aureus isolates, obtained from the same number of patients suffering from bacteremia. Using a bead-based Luminex technique, we measure the patients’ total immunoglobulin G (IgG) against the 7 FnBPA isotypes at the onset and during the time course of bacteremia (median of 10 serum samples per patient over a median of 35 days). A significant increase in IgG against the FnBPA A domain, including the isotype carried by the infecting strain, is observed in only three out of 22 patients (14%) after the onset of bacteremia. Using a Luminex-based FnBPA–fibrinogen-binding assay, we find that preincubation of recombinant FnBPA isotypes with IgG from diverse patients does not interfere with binding to fibrinogen. This observation is confirmed using an alternative Luminex-based assay and enzyme-linked immunosorbent assay (ELISA). IMPORTANCE Despite the many in vitro and murine in vivo studies involving FnBPA, the actual presence of this virulence factor during human infection is less well established. Furthermore, it is currently unknown to what extent sequence variation in such a virulence factor affects the human antibody response and the ability of antibodies to interfere with FnBPA function. This study sheds new light on these issues. First, the uniform presence of a patient’s IgG against FnBPA indicates the presence and importance of this virulence factor during S. aureus pathogenesis. Second, the absence of an increase in antibody production in most patients following bacteremia indicates the complexity of S. aureus-host interactions, possibly involving immune evasion or lack of expression of FnBPA during invasive infection. Finally, we provide new insights into the inability of human antibodies to interfere with FnBPA-fibrinogen binding. These observations should be taken into account during the development of novel vaccination approaches.P. Martijn den ReijerMehri TavakolNicole Lemmens-den ToomDikra AllouchSheila ThomasVannakambadi K. GaneshYa-Ping KoHenri A. VerbrughWillem J. B. van WamelAmerican Society for MicrobiologyarticleStaphylococcus aureusantibody functionantibody repertoirebacteremiafibrinogenfibronectin-binding protein AMicrobiologyQR1-502ENmSphere, Vol 3, Iss 2 (2018) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Staphylococcus aureus antibody function antibody repertoire bacteremia fibrinogen fibronectin-binding protein A Microbiology QR1-502 |
| spellingShingle |
Staphylococcus aureus antibody function antibody repertoire bacteremia fibrinogen fibronectin-binding protein A Microbiology QR1-502 P. Martijn den Reijer Mehri Tavakol Nicole Lemmens-den Toom Dikra Allouch Sheila Thomas Vannakambadi K. Ganesh Ya-Ping Ko Henri A. Verbrugh Willem J. B. van Wamel Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| description |
ABSTRACT The fibronectin-binding protein A (FnBPA) is a cell surface-associated protein of Staphylococcus aureus which mediates adherence to the host extracellular matrix and is important for bacterial virulence. Previously, substantial sequence diversity was found among strains in the fibrinogen-binding A domain of this protein, and 7 different isotypes were described. The effect of this sequence diversity on the human antibody response, in terms of both antibody production and antibody function, remains unclear. In this study, we identify five different FnBPA A domain isotypes based on the sequence results of 22 clinical S. aureus isolates, obtained from the same number of patients suffering from bacteremia. Using a bead-based Luminex technique, we measure the patients’ total immunoglobulin G (IgG) against the 7 FnBPA isotypes at the onset and during the time course of bacteremia (median of 10 serum samples per patient over a median of 35 days). A significant increase in IgG against the FnBPA A domain, including the isotype carried by the infecting strain, is observed in only three out of 22 patients (14%) after the onset of bacteremia. Using a Luminex-based FnBPA–fibrinogen-binding assay, we find that preincubation of recombinant FnBPA isotypes with IgG from diverse patients does not interfere with binding to fibrinogen. This observation is confirmed using an alternative Luminex-based assay and enzyme-linked immunosorbent assay (ELISA). IMPORTANCE Despite the many in vitro and murine in vivo studies involving FnBPA, the actual presence of this virulence factor during human infection is less well established. Furthermore, it is currently unknown to what extent sequence variation in such a virulence factor affects the human antibody response and the ability of antibodies to interfere with FnBPA function. This study sheds new light on these issues. First, the uniform presence of a patient’s IgG against FnBPA indicates the presence and importance of this virulence factor during S. aureus pathogenesis. Second, the absence of an increase in antibody production in most patients following bacteremia indicates the complexity of S. aureus-host interactions, possibly involving immune evasion or lack of expression of FnBPA during invasive infection. Finally, we provide new insights into the inability of human antibodies to interfere with FnBPA-fibrinogen binding. These observations should be taken into account during the development of novel vaccination approaches. |
| format |
article |
| author |
P. Martijn den Reijer Mehri Tavakol Nicole Lemmens-den Toom Dikra Allouch Sheila Thomas Vannakambadi K. Ganesh Ya-Ping Ko Henri A. Verbrugh Willem J. B. van Wamel |
| author_facet |
P. Martijn den Reijer Mehri Tavakol Nicole Lemmens-den Toom Dikra Allouch Sheila Thomas Vannakambadi K. Ganesh Ya-Ping Ko Henri A. Verbrugh Willem J. B. van Wamel |
| author_sort |
P. Martijn den Reijer |
| title |
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| title_short |
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| title_full |
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| title_fullStr |
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| title_full_unstemmed |
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Fibronectin-Binding Protein A |
| title_sort |
human immunoglobulin g cannot inhibit fibrinogen binding by the genetically diverse a domain of <named-content content-type="genus-species">staphylococcus aureus</named-content> fibronectin-binding protein a |
| publisher |
American Society for Microbiology |
| publishDate |
2018 |
| url |
https://doaj.org/article/da1ec3d8e8bb47a68f575bab5078855f |
| work_keys_str_mv |
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