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Mol. Life Sci."],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The opportunistic pathogen\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    has gained precedence over the years due to its ability to develop resistance to existing antibiotics, thereby necessitating alternative strategies to understand and combat the bacterium. Our previous work identified the interaction between the bacterial lectin LecA and its host cell glycosphingolipid receptor globotriaosylceramide (Gb3) as a crucial step for the engulfment of\n                    <jats:italic>P.\u00a0aeruginosa<\/jats:italic>\n                    \u00a0via the lipid zipper mechanism. In this study, we define the LecA-associated host cell membrane domain by pull-down and mass spectrometry analysis. We unraveled a predilection of LecA for binding to saturated, long fatty acyl chain-containing Gb3 species in the extracellular membrane leaflet and an induction of dynamic phosphatidylinositol (3,4,5)-trisphosphate (PIP\n                    <jats:sub>3<\/jats:sub>\n                    ) clusters at the intracellular leaflet co-localizing with sites of LecA binding. We found flotillins and the GPI-anchored protein CD59 not only to be an integral part of the LecA-interacting membrane domain, but also majorly influencing bacterial invasion\u00a0as depletion of either of these host cell proteins resulted in about 50% reduced invasiveness of the\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    strain PAO1. In summary, we report that the LecA-Gb3 interaction at the extracellular leaflet induces the formation of a plasma membrane domain enriched in saturated Gb3 species, CD59, PIP\n                    <jats:sub>3<\/jats:sub>\n                    and flotillin thereby facilitating efficient uptake of PAO1.\n                  <\/jats:p>","DOI":"10.1007\/s00018-021-03766-1","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T07:17:56Z","timestamp":1612855076000},"page":"3637-3656","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Gb3-enriched CD59\/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa"],"prefix":"10.1007","volume":"78","author":[{"given":"Annette","family":"Brandel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-4563","authenticated-orcid":false,"given":"Sahaja","family":"Aigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-1781","authenticated-orcid":false,"given":"Simon","family":"Lagies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Schlimpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Valeria","family":"Mel\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maokai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0367","authenticated-orcid":false,"given":"Daniel","family":"Fisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Madl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Eierhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kammerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-246X","authenticated-orcid":false,"given":"Winfried","family":"R\u00f6mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"3766_CR1","unstructured":"WHO (2017) Global priority list of antibiotic-resistant batceria to guide research, discovery, and development of new antibiotics. 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