Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
16
03
2023
accepted:
16
10
2023
medline:
27
10
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37872209
doi: 10.1038/s41467-023-42572-0
pii: 10.1038/s41467-023-42572-0
pmc: PMC10593946
doi:
Substances chimiques
Bacterial Proteins
0
Immunoglobulin G
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6693Informations de copyright
© 2023. Springer Nature Limited.
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