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Candidiasis represents the third-to-fourth most frequent nosocomial infection worldwide, as this normal commensal of humans causes opportunistic infections in an expanding population of immune- and medically compromised patients. These infections are frequently associated with biofilm formation, which complicates treatment and contributes to unacceptably high mortality rates.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods:<\/jats:title>\n                <jats:p>To address the pressing need for new antifungals, we have performed a high-content screen of 20,000 small molecules in a chemical library (NOVACore) to identify compounds that inhibit <jats:italic>C. albicans<\/jats:italic> biofilm formation, and conducted a series of follow-up studies to examine the <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> activity of the identified compounds.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results:<\/jats:title>\n                <jats:p>The screen identified a novel series of diazaspiro-decane structural analogs that were largely represented among the bioactive compounds. Characterization of the leading compound from this series indicated that it inhibits processes associated with <jats:italic>C. albicans<\/jats:italic> virulence, most notably biofilm formation and filamentation, without having an effect on overall growth or eliciting resistance. This compound demonstrated <jats:italic>in vivo<\/jats:italic> activity in clinically relevant murine models of both invasive and oral candidiasis and as such represents a promising lead for antifungal drug development. Furthermore, these results provide proof of concept for the implementation of antivirulence approaches against <jats:italic>C. albicans<\/jats:italic> and other fungal infections that would be less likely to foster the emergence of resistance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/npjbiofilms.2015.12","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T16:01:38Z","timestamp":1439308898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["A novel small molecule inhibitor of Candida albicans biofilm formation, filamentation and virulence with low potential for the development of resistance"],"prefix":"10.1038","volume":"1","author":[{"given":"Christopher G","family":"Pierce","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok K","family":"Chaturvedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L","family":"Lazzell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P","family":"Saville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanton F","family":"McHardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L","family":"Lopez-Ribot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,12]]},"reference":[{"key":"BFnpjbiofilms201512_CR1","doi-asserted-by":"publisher","first-page":"165rv113","DOI":"10.1126\/scitranslmed.3004404","volume":"4","author":"GD Brown","year":"2012","unstructured":"Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC . 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