{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:31:32Z","timestamp":1792441892257,"version":"4.5.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["CRSI33_130016"],"award-info":[{"award-number":["CRSI33_130016"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_172951"],"award-info":[{"award-number":["31003A_172951"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Klebsiella pneumoniae<\/jats:italic> is the causative agent of a variety of severe infections. Many <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> strains are resistant to multiple antibiotics, and this situation creates a need for new antibacterial molecules. <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> pathogenicity relies largely on its ability to escape phagocytosis and intracellular killing by phagocytic cells. Interfering with these escape mechanisms may allow to decrease bacterial virulence and to combat infections. In this study, we used <jats:italic>Dictyostelium discoideum<\/jats:italic> as a model phagocyte to screen a collection of 1,099 chemical compounds. <jats:italic>Phg1A<\/jats:italic> KO <jats:italic>D<\/jats:italic>. <jats:italic>discoideum<\/jats:italic> cells cannot feed upon <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> bacteria, unless bacteria bear mutations decreasing their virulence. We identified 3 non-antibiotic compounds that restored growth of <jats:italic>phg1A<\/jats:italic> KO cells on <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic>, and we characterized the mode of action of one of them, 5-ethyl-2\u2019-deoxyuridine (K2). K2-treated bacteria were more rapidly killed in <jats:italic>D<\/jats:italic>. <jats:italic>discoideum<\/jats:italic> phagosomes than non-treated bacteria. They were more sensitive to polymyxin and their outer membrane was more accessible to a hydrophobic fluorescent probe. These results suggest that K2 acts by rendering the membrane of <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> accessible to antibacterial effectors. K2 was effective on three different <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> strains, and acted at concentrations as low as 3 \u03bcM. K2 has previously been used to treat viral infections but its precise molecular mechanism of action in <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> remains to be determined.<\/jats:p>","DOI":"10.1371\/journal.pone.0269093","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T17:46:52Z","timestamp":1667238412000},"page":"e0269093","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["5-ethyl-2\u2019-deoxyuridine fragilizes Klebsiella pneumoniae outer wall and facilitates intracellular killing by phagocytic cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Estelle","family":"Ifrid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajer","family":"Ouertatani-Sakouhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Jauslin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Kicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"Chiriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Hilbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1079-648X","authenticated-orcid":true,"given":"Leonardo","family":"Scapozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Soldati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-0358","authenticated-orcid":true,"given":"Pierre","family":"Cosson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"pone.0269093.ref001","doi-asserted-by":"crossref","first-page":"105833","DOI":"10.1016\/j.ijantimicag.2019.10.014","article-title":"A systematic review and meta-analysis of treatment outcomes following antibiotic therapy among patients with carbapenem-resistant Klebsiella pneumoniae infections","volume":"55","author":"AA Agyeman","year":"2019","journal-title":"Int J Antimicrob Agents"},{"key":"pone.0269093.ref002","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2201","article-title":"Drugs for bad bugs: confronting the challenges of antibacterial discovery","volume":"6","author":"DJ Payne","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"pone.0269093.ref003","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nrmicro1818","article-title":"The biology and future prospects of antivirulence therapies","volume":"6","author":"L Cegelski","year":"2008","journal-title":"Nat Rev Microbiol"},{"key":"pone.0269093.ref004","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1128\/JB.184.11.3027-3033.2002","article-title":"Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system","volume":"184","author":"P Cosson","year":"2002","journal-title":"J Bacteriol"},{"key":"pone.0269093.ref005","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fcimb.2018.00061","article-title":"Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection.","volume":"8","author":"AL Swart","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0269093.ref006","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3389\/fcimb.2017.00529","article-title":"When Dicty Met Myco, a (Not So) Romantic Story about One Amoeba and Its Intracellular Pathogen.","volume":"7","author":"E Cardenal-Munoz","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0269093.ref007","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1387\/ijdb.190128sb","article-title":"The past, present and future of Dictyostelium as a model system","volume":"63","author":"S. 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