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In contrast to target-focused approaches, antivirulence phenotypic screens enable identification of bioactive molecules that induce a desirable biological readout without making\n                    <jats:italic>a priori<\/jats:italic>\n                    assumption about the cellular target. Here, we screened a chemical library of 678 small molecules against the invasive hyphal growth of the human opportunistic yeast\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . We found that a halogenated salicylanilide (N1-(3,5-dichlorophenyl)-5-chloro-2-hydroxybenzamide) and one of its analogs, Niclosamide, an FDA-approved anthelmintic in humans, exhibited both antifilamentation and antibiofilm activities against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    and the multi-resistant yeast\n                    <jats:italic>C. auris<\/jats:italic>\n                    . The antivirulence activity of halogenated salicylanilides were also expanded to\n                    <jats:italic>C. albicans<\/jats:italic>\n                    resistant strains with different resistance mechanisms. We also found that Niclosamide protected the intestinal epithelial cells against invasion by\n                    <jats:italic>C. albicans<\/jats:italic>\n                    . Transcriptional profiling of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    challenged with Niclosamide exhibited a signature that is characteristic of the mitochondria-to-nucleus retrograde response. Our chemogenomic analysis showed that halogenated salicylanilides compromise the potential-dependant mitochondrial protein translocon machinery. Given the fact that the safety of Niclosamide is well established in humans, this molecule could represent the first clinically approved antivirulence agent against a pathogenic fungus.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-29973-8","type":"journal-article","created":{"date-parts":[[2018,7,26]],"date-time":"2018-07-26T06:58:09Z","timestamp":1532588289000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["A phenotypic small-molecule screen identifies halogenated salicylanilides as inhibitors of fungal morphogenesis, biofilm formation and host cell invasion"],"prefix":"10.1038","volume":"8","author":[{"given":"Carlos","family":"Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Burgain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Chaillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9milie","family":"Pic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Khemiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0506-7752","authenticated-orcid":false,"given":"Adnane","family":"Sellam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,1]]},"reference":[{"key":"29973_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1128\/CMR.00029-06","volume":"20","author":"MA Pfaller","year":"2007","unstructured":"Pfaller, M. A. & Diekema, D. J. Epidemiology of invasive candidiasis: a persistent public health problem. Clinical microbiology reviews 20, 133\u2013163, https:\/\/doi.org\/10.1128\/CMR.00029-06 (2007).","journal-title":"Clinical microbiology reviews"},{"key":"29973_CR2","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1086\/378745","volume":"37","author":"O Gudlaugsson","year":"2003","unstructured":"Gudlaugsson, O. et al. Attributable mortality of nosocomial candidemia, revisited. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 37, 1172\u20131177, https:\/\/doi.org\/10.1086\/378745 (2003).","journal-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America"},{"key":"29973_CR3","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1086\/596757","volume":"48","author":"PG Pappas","year":"2009","unstructured":"Pappas, P. G. et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 48, 503\u2013535, https:\/\/doi.org\/10.1086\/596757 (2009).","journal-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America"},{"key":"29973_CR4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1128\/MMBR.00045-10","volume":"75","author":"RS Shapiro","year":"2011","unstructured":"Shapiro, R. S., Robbins, N. & Cowen, L. E. Regulatory circuitry governing fungal development, drug resistance, and disease. 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