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In recent decades, fungal infections have incredibly increased with  Candida  genus as the major cause of morbidity and mortality in hospitalized and immunocompromised patients. Most of the  Candida  species are proficient in biofilm formation on implanted medical devices as well as human tissues. Biofilm related  Candida  infections are very difficult to treat using common antifungal agents owing to their increased drug resistance. To address these issues, the present study investigated the antibiofilm and antivirulent properties of  Syzygium cumini  derived quinic acid in combination with known antifungal compound undecanoic acid. Initially, antibiofilm potential of  S. cumini  leaf extract was assessed and the active principles were identified through gas chromatography and mass spectrometry analysis. Among the compounds identified, quinic acid was one of the major compounds. The interaction between quinic acid and undecanoic acid was found to be synergistic in the Fractional inhibitory concentration index (≤0.5). Results of  in vitro  assays and gene expression analysis suggested that the synergistic combinations of quinic acid and undecanoic acid significantly inhibited virulence traits of  Candida  spp. such as the biofilm formation, yeast-to-hyphal transition, extracellular polymeric substances production, filamentation, secreted hydrolases production and ergosterol biosynthesis. In addition, result of  in vivo  studies using  Caenorhabditis elegans  demonstrated the non-toxic nature of QA-UDA combination and antivirulence effect against  Candida  spp. For the first time, synergistic antivirulence ability of quinic acid and undecanoic acid was explored against  Candida  spp. Thus, results obtained from the present study suggest that combination of phytochemicals might be used an alternate therapeutic strategy for the prevention and treatment of biofilm associated  Candida  infection.

Synergistic Effect of Quinic Acid Derived From Syzygium cumini and Undecanoic Acid Against Candida spp. Biofilm and Virulence