Inhibitory Effect of Morin Against Candida albicans Pathogenicity and Virulence Factor Production: An in vitro and in vivo Approaches.

Ravindran Durgadevi,Rajaiah Alexpandi,Arunachalam Kannappan,Arumugam Veera Ravi,Gurusamy Abirami

doi:10.3389/fmicb.2020.561298

Ravindran Durgadevi, Rajaiah Alexpandi + Show 3 more

Open Access

https://doi.org/10.3389/fmicb.2020.561298

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Abstract

Candida albicans is considered an exclusive etiologic agent of candidiasis, a very common fungal infection in human. The expression of virulence factors contributes highly to the pathogenicity of C. albicans. These factors include biofilm formation, yeast-to-hyphal transition, adhesins, aspartyl proteases, and phospholipases secretion. Moreover, resistance development is a critical issue for the therapeutic failure of antifungal agents against systemic candidiasis. To circumvent resistance development, the present study investigated the virulence targeted therapeutic activity of the phyto-bioactive compound morin against C. albicans. Morin is a natural compound commonly found in medicinal plants and widely used in the pharmaceutical and cosmetic products/industries. The present study explicated the significant inhibitory potential of morin against biofilm formation and other virulence factors’ production, such as yeast-hyphal formation, phospholipase, and exopolymeric substances, in C. albicans. Further, qPCR analysis confirmed the downregulation of biofilm and virlence-related genes in C. albicans upon morin treatment, which is in correspondence with the in vitro bioassays. Further, the docking analysis revealed that morin shows strong affinity with Hwp-1 protein, which regulates the expression of biofilm and hyphal formation in C. albicans and, thereby, abolishes fungal pathogenicity. Moreover, the anti-infective potential of morin against C. albicans-associated systemic candidiasis is confirmed through an in vivo approach using biomedical model organism zebrafish (Danio rerio). The outcomes of the in vivo study demonstrate that the morin treatment effectively rescues animals from C. albicans infections and extends their survival rate by inhibiting the internal colonization of C. albicans. Histopathology analysis revealed extensive candidiasis-related pathognomonic changes in the gills, intestine, and kidney of animals infected with C. albicans, while no extensive abnormalities were observed in morin-treated animals. The results evidenced that morin has the ability to protect against the pathognomonic effect and histopathological lesions caused by C. albicans infection in zebrafish. Thus, the present study suggests that the utilization of morin could act as a potent therapeutic medication for C. albicans instigated candidiasis.

Highlights

Candida albicans is an opportunistic fungal pathogen responsible for about 50–90% of all cases of candidiasis in humans
The effect of morin on C. albicans growth was observed by microbroth dilution method, which showed the non-antifungal nature of morin up to 600 μg/ml concentration (Figure 1A)
Based on the present study, it could be concluded that morin treatment significantly inhibited the biofilm formation of C. albicans in a concentration-dependent manner

Summary

Introduction

Candida albicans is an opportunistic fungal pathogen responsible for about 50–90% of all cases of candidiasis in humans. The pathogenicity of C. albicans is aided by its exclusive virulence factors’ production such as biofilm formation, yeast-hyphal formation, and secretion of proteolytic and lipolytic enzymes (Galocha et al, 2019). Among these virulent features, biofilm formation is imperious for C. albicans pathogenicity (Mohandas and Ballal, 2011). The occurrence of invasive candidiasis in indwelling implant devices, such as catheters and stents, leads to persistent candidemia (Nucci, 2011). Biofilms have reduced susceptibility to antifungal drug therapy and host immune responses (da Costa et al, 2009)

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