{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:57:14Z","timestamp":1790301434719,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["16GW0213"],"award-info":[{"award-number":["16GW0213"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The environmental bacterium Legionella pneumophila is an intracellular pathogen of various protozoan hosts and able to cause Legionnaires\u2019 disease, a severe pneumonia in humans. By encoding a wide selection of virulence factors, the infectious agent possesses several strategies to manipulate its host cells and evade immune detection. In the present study, we demonstrate that the L. pneumophila zinc metalloprotease ProA functions as a modulator of flagellin-mediated TLR5 stimulation and subsequent activation of the pro-inflammatory NF-\u03baB pathway. We found ProA to be capable of directly degrading immunogenic FlaA monomers but not the polymeric form of bacterial flagella. These results indicate a role of the protease in antagonizing immune stimulation, which was further substantiated in HEK-BlueTM hTLR5 Detection assays. Addition of purified proteins, bacterial suspensions of L. pneumophila mutant strains as well as supernatants of human lung tissue explant infection to this reporter cell line demonstrated that ProA specifically decreases the TLR5 response via FlaA degradation. Conclusively, the zinc metalloprotease ProA serves as a powerful regulator of exogenous flagellin and presumably creates an important advantage for L. pneumophila proliferation in mammalian hosts by promoting immune evasion.<\/jats:p>","DOI":"10.3390\/biom12050624","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T08:14:06Z","timestamp":1650701646000},"page":"624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Zinc Metalloprotease ProA from Legionella pneumophila Inhibits the Pro-Inflammatory Host Response by Degradation of Bacterial Flagellin"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8084","authenticated-orcid":false,"given":"Lina","family":"Scheithauer","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie, Technische Universit\u00e4t Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-6759","authenticated-orcid":false,"given":"Stefanie","family":"Thiem","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie, Technische Universit\u00e4t Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can M.","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie, Technische Universit\u00e4t Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Dellmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, St\u00e4dtisches Klinikum Braunschweig, Celler Stra\u00dfe 38, 38114 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Steinert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Mikrobiologie, Technische Universit\u00e4t Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany"},{"name":"Helmholtz Center for Infection Research, Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1056\/NEJM197712012972201","article-title":"Legionnaires\u2019 disease: Description of an epidemic of pneumonia","volume":"297","author":"Fraser","year":"1977","journal-title":"N. 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