Screening the «Pathogen Box» for the Identification of Candida albicans Biofilm Inhibitors.

Related Articles

Screening the "Pathogen Box" for the Identification of Candida albicans Biofilm Inhibitors.

Antimicrob Agents Chemother. 2016 Oct 24;:

Authors: Vila T, Lopez-Ribot JL

Abstract
Candida albicans remains the main causative agent of candidiasis, one of the most frequent nosocomial infections, with unacceptably high mortality rates. Biofilm formation is a major risk factor for invasive candidiasis as Candida biofilms display high level resistance to most antifungal agents. In this work we have screened the Pathogen Box® chemical library (Medicines for Malaria Venture - MMV, Switzerland) in search for inhibitors of C. albicans biofilm formation. Our initial screen identified seven hits, and additional dose-response assays confirmed the biofilm-inhibitory activity of six of these small molecules. Three compounds, MMV688768, MMV687273 and MMV687807, were also able to reduce the metabolic activity of cells within pre-formed biofilms. Interestingly, the most potent of these, compound MMV688768, displayed increased anti-biofilm activity as compared to its activity against planktonic cultures, indicating that it may affect processes with a predominant role during the biofilm mode of growth. This compound demonstrated a high selectivity index when its anti-biofilm activity was compared with its toxicity in liver hepatocellular cells. In vitro combination assays showed a synergistic interaction between compound MMV688768 and fluconazole against preformed biofilms. Overall our results indicate that this compound may constitute a potential candidate for further clinical development.

PMID: 27795383 [PubMed - as supplied by publisher]