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Pathogen-driven deg...
Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections
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- Toledo, Alejandro Gomez (author)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Bratanis, Eleni (author)
- Lund University,Lunds universitet,Immunmodulerande effekter av blodplättar vid inflammation och infektion,Forskargrupper vid Lunds universitet,epIgG,Immunomodulatory effects of platelets during inflammation and infection,Lund University Research Groups
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- Velásquez, Erika (author)
- Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups
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- Chowdhury, Sounak (author)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Olofsson, Berit (author)
- Lund University,Lunds universitet,Kvantitativ immunbiologi,Forskargrupper vid Lunds universitet,epIgG,Quantitative immunobiology,Lund University Research Groups
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- Sorrentino, James T (author)
- University of California, San Diego
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- Karlsson, Christofer (author)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Lewis, Nathan E (author)
- University of California, San Diego
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- Esko, Jeffrey D (author)
- University of California, San Diego
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- Collin, Mattias (author)
- Lund University,Lunds universitet,Infektion och immunmodulering,Forskargrupper vid Lunds universitet,Infection and immunomodulation,Lund University Research Groups
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- Shannon, Oonagh (author)
- Lund University,Lunds universitet,Immunmodulerande effekter av blodplättar vid inflammation och infektion,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,Immunomodulatory effects of platelets during inflammation and infection,Lund University Research Groups
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- Malmström, Johan (author)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Lund University Research Groups,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Communications. - 2041-1723. ; 14, s. 1-16
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Toledo, Alejandr ...
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Bratanis, Eleni
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Velásquez, Erika
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Chowdhury, Souna ...
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Olofsson, Berit
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Sorrentino, Jame ...
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show more...
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Karlsson, Christ ...
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Lewis, Nathan E
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Esko, Jeffrey D
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Collin, Mattias
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Shannon, Oonagh
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Malmström, Johan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University