{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:08:57Z","timestamp":1789625337908,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010447","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"biotechnology and biological sciences research council","doi-asserted-by":"publisher","award":["BB\/M018318\/1"],"award-info":[{"award-number":["BB\/M018318\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["056232"],"award-info":[{"award-number":["056232"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The pathogenic bacterium<jats:italic>Yersina pestis<\/jats:italic>is protected from macrophage engulfment by a capsule like antigen, F1, formed of long polymers of the monomer protein, Caf1. However, despite the importance of this pathogen, the mechanism of protection was not understood. Here we demonstrate how F1 protects the bacteria from phagocytosis. First, we show that<jats:italic>Escherichia coli<\/jats:italic>expressing F1 showed greatly reduced adherence to macrophages. Furthermore, the few cells that did adhere remained on the macrophage surface and were not engulfed. We then inserted, by mutation, an \u201cRGDS\u201d integrin binding motif into Caf1. This did not change the number of cells adhering to macrophages but increased the fraction of adherent cells that were engulfed. Therefore, F1 protects in two separate ways, reducing cell adhesion, possibly by acting as a polymer brush, and hiding innate receptor binding sites needed for engulfment. F1 is very robust and we show that<jats:italic>E<\/jats:italic>.<jats:italic>coli<\/jats:italic>expressing weakened mutant polymers are engulfed like the RGDS mutant. This suggests that innate attachment sites on the native cell surface are exposed if F1 is weakened. Single-molecule force spectroscopy (SMFS) experiments revealed that wild-type F1 displays a very high mechanical stability of 400 pN. However, the mechanical resistance of the destabilised mutants, that were fully engulfed, was only 20% weaker. By only marginally exceeding the mechanical force applied to the Caf1 polymer during phagocytosis it may be that the exceptional tensile strength evolved to resist the forces applied at this stage of engulfment.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010447","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T18:09:45Z","timestamp":1648750185000},"page":"e1010447","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Unraveling the molecular determinants of the anti-phagocytic protein cloak of plague bacteria"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-195X","authenticated-orcid":true,"given":"Daniel T.","family":"Peters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Reifs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-2562","authenticated-orcid":true,"given":"Alvaro","family":"Alonso-Caballero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzeldin","family":"Madkour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Waller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-6585","authenticated-orcid":true,"given":"Brendan","family":"Kenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Perez-Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-9085","authenticated-orcid":true,"given":"Jeremy H.","family":"Lakey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"1","key":"ppat.1010447.ref001","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev-pathol-011811-132445","article-title":"The Cell Biology of Phagocytosis","volume":"7","author":"RS Flannagan","year":"2012","journal-title":"Annual Review of Pathology: Mechanisms of Disease"},{"issue":"3","key":"ppat.1010447.ref002","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2016.02.026","article-title":"Phagocytosis: An Immunobiologic Process","volume":"44","author":"S. 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