Anticandidal Activity of Kalopanaxsaponin A: Effect on Proliferation, Cell Morphology, and Key Virulence Attributes of Candida albicans.

Ying Li,Huankai Yao,Hongchun Li,Zuobin Zhu,Mingju Yan,Mingzhu Shan,Yuechen Wang,Bing Gu

doi:10.3389/fmicb.2019.02844

Abstract

BackgroundThe pathogenicity of Candida albicans is attributed to various virulence factors including adhesion to the surface of epithelial cells or mucosa, germ tube formation, hyphal morphogenesis, development of drug resistant biofilms, and so on. The objective of this study was to investigate the effects of Kalopanaxsaponin A (KPA) on the virulence of C. albicans.MethodsThe effect of KPA on the virulence of C. albicans was characterized by an XTT reduction assay and fluorescent microscopic observation. The action mechanism was further explored using GC/MS system and BioTek Synergy2 spectrofluorophotometry. The cytotoxicity and therapeutic effect of KPA were evaluated by the Caenorhabditis elegans-C. albicans infection model in vivo.ResultsThe minimum inhibitory concentration (MIC) of KPA was 8∼16 μg/mL for various genotypes of C. albicans. The compound was identified as having remarkable effect on the adhesion, morphological transition and biofilm formation of C. albicans. The results of fluorescent microscopy and GC/MS system suggested that KPA could promote the secretion of farnesol by regulating the expression of Dpp3 and decrease the intracellular cAMP level, which together inhibited morphological transition and biofilm formation. Notably, KPA showed low toxicity in vivo and a low possibility of developing resistance.ConclusionOur results demonstrated that KPA had remarkable efficacy against C. albicans pathogenicity, suggesting that it could be a potential option for the clinical treatment of candidiasis.

Highlights

Candida albicans is a component of the normal flora of healthy human beings, residing on mucosal surfaces and in the gastrointestinal and genitourinary tracts (Ganguly and Mitchell, 2011)
The results of fluorescent microscopy and GC/MS system suggested that Kalopanaxsaponin A (KPA) could promote the secretion of farnesol by regulating the expression of Dpp3 and decrease the intracellular cyclic adenosine monophosphate (cAMP) level, which together inhibited morphological transition and biofilm formation
Our results demonstrated that KPA had remarkable efficacy against C. albicans pathogenicity, suggesting that it could be a potential option for the clinical treatment of candidiasis

Summary

Introduction

Candida albicans is a component of the normal flora of healthy human beings, residing on mucosal surfaces and in the gastrointestinal and genitourinary tracts (Ganguly and Mitchell, 2011). In the United States, C. albicans is the fourth most common microbe causing blood infections with a crude mortality rate of about 50% (Haynes, 2002; Pfaller and Diekema, 2007). With the increasing severe situation of C. albicans infection, antifungal agents have been developed and widely used in the treatment of various C. albicans infections. Resistance has become a challenge in the clinical treatment of C. albicans infections due to wide use or even abuse of antifungal drugs in the recent decade. It is an urgent task to develop new drugs against C. albicans resistant infections (Haque et al, 2016). The pathogenicity of Candida albicans is attributed to various virulence factors including adhesion to the surface of epithelial cells or mucosa, germ tube formation, hyphal morphogenesis, development of drug resistant biofilms, and so on. The objective of this study was to investigate the effects of Kalopanaxsaponin A (KPA) on the virulence of C. albicans

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