Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections
(2023) In Nature Communications 14. p.1-16- Abstract
Group A streptococcus (GAS) is a major bacterial pathogen responsible for both local and systemic infections in humans. The molecular mechanisms that contribute to disease heterogeneity remain poorly understood. Here we show that the transition from a local to a systemic GAS infection is paralleled by pathogen-driven alterations in IgG homeostasis. Using animal models and a combination of sensitive proteomics and glycoproteomics readouts, we documented the progressive accumulation of IgG cleavage products in plasma, due to extensive enzymatic degradation triggered by GAS infection in vivo. The level of IgG degradation was modulated by the route of pathogen inoculation, and mechanistically linked to the combined activities of the... (More)
Group A streptococcus (GAS) is a major bacterial pathogen responsible for both local and systemic infections in humans. The molecular mechanisms that contribute to disease heterogeneity remain poorly understood. Here we show that the transition from a local to a systemic GAS infection is paralleled by pathogen-driven alterations in IgG homeostasis. Using animal models and a combination of sensitive proteomics and glycoproteomics readouts, we documented the progressive accumulation of IgG cleavage products in plasma, due to extensive enzymatic degradation triggered by GAS infection in vivo. The level of IgG degradation was modulated by the route of pathogen inoculation, and mechanistically linked to the combined activities of the bacterial protease IdeS and the endoglycosidase EndoS, upregulated during infection. Importantly, we show that these virulence factors can alter the structure and function of exogenous therapeutic IgG in vivo. These results shed light on the role of bacterial virulence factors in shaping GAS pathogenesis, and potentially blunting the efficacy of antimicrobial therapies.
(Less)
- author
- organization
-
- Infection Medicine Proteomics (research group)
- epIgG (research group)
- Immunomodulatory effects of platelets during inflammation and infection (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- IPSC Laboratory for CNS Disease Modeling (research group)
- Quantitative immunobiology (research group)
- Infection and immunomodulation (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- LTH Profile Area: Engineering Health
- BioMS (research group)
- publishing date
- 2023-10-23
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 14
- article number
- 6693
- pages
- 1 - 16
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85174676240
- pmid:37872209
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-023-42572-0
- language
- English
- LU publication?
- yes
- additional info
- © 2023. Springer Nature Limited.
- id
- 58b4227d-6d78-4b76-a59d-f1d358d16f3f
- date added to LUP
- 2023-10-25 18:06:57
- date last changed
- 2024-04-15 17:37:19
@article{58b4227d-6d78-4b76-a59d-f1d358d16f3f, abstract = {{<p>Group A streptococcus (GAS) is a major bacterial pathogen responsible for both local and systemic infections in humans. The molecular mechanisms that contribute to disease heterogeneity remain poorly understood. Here we show that the transition from a local to a systemic GAS infection is paralleled by pathogen-driven alterations in IgG homeostasis. Using animal models and a combination of sensitive proteomics and glycoproteomics readouts, we documented the progressive accumulation of IgG cleavage products in plasma, due to extensive enzymatic degradation triggered by GAS infection in vivo. The level of IgG degradation was modulated by the route of pathogen inoculation, and mechanistically linked to the combined activities of the bacterial protease IdeS and the endoglycosidase EndoS, upregulated during infection. Importantly, we show that these virulence factors can alter the structure and function of exogenous therapeutic IgG in vivo. These results shed light on the role of bacterial virulence factors in shaping GAS pathogenesis, and potentially blunting the efficacy of antimicrobial therapies.</p>}}, author = {{Toledo, Alejandro Gomez and Bratanis, Eleni and Velásquez, Erika and Chowdhury, Sounak and Olofsson, Berit and Sorrentino, James T and Karlsson, Christofer and Lewis, Nathan E and Esko, Jeffrey D and Collin, Mattias and Shannon, Oonagh and Malmström, Johan}}, issn = {{2041-1723}}, language = {{eng}}, month = {{10}}, pages = {{1--16}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections}}, url = {{http://dx.doi.org/10.1038/s41467-023-42572-0}}, doi = {{10.1038/s41467-023-42572-0}}, volume = {{14}}, year = {{2023}}, }