Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections.
Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections.
复制标题
DOI：
10.1038/s41467-023-42572-0
复制
发表时间：
2023-10-23
影响因子：
16.6
通讯作者：
Malmstrom, Johan
中科院分区：
文献类型：
--
作者：
Toledo, Alejandro Gomez;Bratanis, Eleni;Velasquez, Erika;Chowdhury, Sounak;Olofsson, Berit;Sorrentino, James T.;Karlsson, Christofer;Lewis, Nathan E.;Esko, Jeffrey D.;Collin, Mattias;Shannon, Oonagh;Malmstrom, Johan
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. Group A streptococcus causes a wide range of human diseases and significantly contributes to morbidity and mortality worldwide. Here, Toledo et al show how streptococcus alters the structure and function of endogenous and therapeutic antibodies during infection and how this is affected by the host microenvironment.
登录
查看更多内容
影响因子：
4.6
作者：
Zaytseva OO;Jansen BC;Hanić M;Mrčela M;Razdorov G;Stojković R;Erhardt J;Brizić I;Jonjić S;Pezer M;Lauc G
通讯作者：
Lauc G
影响因子：
3.5
作者：
Castro SA;Dorfmueller HC
通讯作者：
Dorfmueller HC
影响因子：
11.1
作者：
通讯作者：
--
影响因子：
3.8
作者：
Dalton, Tracy L.;Hobb, Rhonda I.;Scott, June R.
通讯作者：
Scott, June R.
影响因子：
--
作者：
Nandakumar, Kutty Selva;Johansson, Bjorn P.;Holmdahl, Rikard
通讯作者：
Holmdahl, Rikard