{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:46:24Z","timestamp":1773769584822,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Glaesserella parasuis<\/jats:italic> causes Gl\u00e4sser\u2019s disease, which is associated with severe polyarthritis, fibrinous polyserositis and meningitis, and leads to significant economic losses to the swine industry worldwide. IgA is one of the most important humoral immune factors present on mucosal surfaces, and it plays a crucial role in neutralizing and removing pathogens. <jats:italic>G. parasuis<\/jats:italic> is able to colonize the mucosal membrane of respiratory tract without being eliminated. Nevertheless, the immune evasion mechanism of <jats:italic>G. parasuis<\/jats:italic> in thwarting IgA remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The object of this study is to characterize the IgA degradation activity of Mac-1-containing autotransporter EspP1 and EspP2 from <jats:italic>G. parasuis<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The swine IgA was purified and incubated with EspP1 and EspP2 respectively. Western blotting was used to detect the cleavage of swine IgA. Generation of EspP1 and EspP2 mutant protein were used to explore the putative active sites of EspPs. LC-MS\/MS based N\/C-terminal sequencing was performed to measure the cleavage sites in swine IgA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Our results show that <jats:italic>G. parasuis<\/jats:italic> EspP1 and EspP2 cleave swine IgA in a dose- and time- dependent manner. <jats:italic>G. parasuis<\/jats:italic> lose the IgA protease activity after simultaneously delete <jats:italic>espP1<\/jats:italic> and <jats:italic>espP2<\/jats:italic> indicating that EspP1 and EspP2 are the only two IgA proteases in <jats:italic>G. parasuis<\/jats:italic>. The IgA protease activity of EspP1 and EspP2 is affected by the putative active sites which contain Cys47, His172 and Asp194\/195. Swine IgA is cleaved within C\u03b11 and C\u03b13 domains upon incubation with EspPs. Moreover, EspPs can degrade neither IgG nor IgM while <jats:italic>G. parasuis<\/jats:italic> possess the ability to degrade IgM unexpectedly. It suggests that <jats:italic>G. parasuis<\/jats:italic> can secrete other proteases to cleave IgM which have never been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report for the first time that both EspP1 and EspP2 are novel IgA-specific proteases and cleave swine IgA within the C\u03b11 and C\u03b13 domains. These findings provide a theoretical basis for the EspPs-induced immune evasion.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1041774","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T06:23:00Z","timestamp":1671085380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Glaesserella parasuis autotransporters EspP1 and EspP2 are novel IgA-specific proteases"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhichao","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunxue","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siting","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qigai","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuwang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.str.2005.10.012","article-title":"Crystal structure of group a Streptococcus Mac-1: insight into dimer-mediated specificity for recognition of human IgG","volume":"14","author":"Agniswamy","year":"2006","journal-title":"Structure"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"108487","DOI":"10.1016\/j.vetmic.2019.108487","article-title":"Mannheimia haemolytica IgA-specific proteases","volume":"239","author":"Ayalew","year":"2019","journal-title":"Vet. 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