Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound
(2023) In Frontiers in Microbiology 14.- Abstract
Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS’ M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies (Abs) circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen’s evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead,... (More)
Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS’ M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies (Abs) circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen’s evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead, they have been found to additionally bind Fn via the A-B domains of their M proteins. Here, we show that human Abs can induce increased Fn-binding affinity in M proteins, likely by enhancing the weak A-B domain binding. We found that this enhanced Fn binding leads to a reduction in Ab-mediated phagocytosis, indicating that this constitutes a GAS immune escape mechanism. We could show that the Fc domain of Abs is necessary to trigger this phenomenon and that Ab flexibility may also play a key role. We, moreover, saw that our Abs could enhance Fn binding in 3 out of 5 emm type strains tested, belonging to different clades, making it likely that this is a more generalizable phenomenon. Together our results suggest a novel synergistic interplay of GAS and host proteins which ultimately benefits the bacterium.
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- author
- Wrighton, Sebastian LU ; Ahnlide, Vibha Kumra LU ; André, Oscar LU ; Bahnan, Wael LU and Nordenfelt, Pontus LU
- organization
-
- epIgG (research group)
- Infection Medicine (BMC)
- Quantitative immunobiology (research group)
- LU Profile Area: Light and Materials
- LTH Profile Area: Nanoscience and Semiconductor Technology
- NanoLund: Centre for Nanoscience
- LTH Profile Area: Photon Science and Technology
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- publishing date
- 2023-01-26
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- adaptive immunity, antibodies, co-evolution, fibronectin, group A – beta hemolytic streptococcus, immune subversion
- in
- Frontiers in Microbiology
- volume
- 14
- article number
- 1069789
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:36778879
- scopus:85147704968
- ISSN
- 1664-302X
- DOI
- 10.3389/fmicb.2023.1069789
- language
- English
- LU publication?
- yes
- id
- 8afe3421-4a56-4bde-b4d4-191375686e69
- date added to LUP
- 2023-02-23 14:17:40
- date last changed
- 2024-12-13 20:30:31
@article{8afe3421-4a56-4bde-b4d4-191375686e69, abstract = {{<p>Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS’ M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies (Abs) circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen’s evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead, they have been found to additionally bind Fn via the A-B domains of their M proteins. Here, we show that human Abs can induce increased Fn-binding affinity in M proteins, likely by enhancing the weak A-B domain binding. We found that this enhanced Fn binding leads to a reduction in Ab-mediated phagocytosis, indicating that this constitutes a GAS immune escape mechanism. We could show that the Fc domain of Abs is necessary to trigger this phenomenon and that Ab flexibility may also play a key role. We, moreover, saw that our Abs could enhance Fn binding in 3 out of 5 emm type strains tested, belonging to different clades, making it likely that this is a more generalizable phenomenon. Together our results suggest a novel synergistic interplay of GAS and host proteins which ultimately benefits the bacterium.</p>}}, author = {{Wrighton, Sebastian and Ahnlide, Vibha Kumra and André, Oscar and Bahnan, Wael and Nordenfelt, Pontus}}, issn = {{1664-302X}}, keywords = {{adaptive immunity; antibodies; co-evolution; fibronectin; group A – beta hemolytic streptococcus; immune subversion}}, language = {{eng}}, month = {{01}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Microbiology}}, title = {{Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound}}, url = {{http://dx.doi.org/10.3389/fmicb.2023.1069789}}, doi = {{10.3389/fmicb.2023.1069789}}, volume = {{14}}, year = {{2023}}, }