Abstract
The incidence of fungal infections has significantly increased in recent years due to the emergence of antifungal resistance. Biofilm formation is considered to be a major contributor to both the infectious diseases and to antimicrobial resistance. Consequently, biofilm-associated infections are often problematic to treat with existing therapeutics. Adhesion of C. albicans to the host surface or implanted materials followed by hyphal invasion and biofilm formation enhances C. albicans pathogenicity and virulence. Thus, developing a therapeutic agent that inhibits candidal adherence, biofilm development and morphological switching could improve clinical management of infections. The present investigation studied two emerging and alternatives strategies, namely antibiofilm and combinatorial approach, to attenuate biofilm formation and the expression of Candida virulence factors. Piperine and thymol are major bioactive components of pepper and thyme, respectively. These phytochemicals are known to possess numerous biological activities, including recently reported antibiofilm effects against C. albicans. The minimum biofilm inhibitory concentration (MBIC) of both phytochemicals was determined to be 32 µg/ml. The phytochemical treatment of Candida biofilms using piperine and thymol revealed synergistic effects at four different combinations of concentrations, i.e. 8 and 8, 8 and 4, 8 and 2 and 4 and 8 µg/ml. These synergistic combinations resulted in the significant reduction in adherence of Candida, hyphal extension and morphological transformation. Moreover, limited exposure of synergistic combinations controlled the hyphal elongation. Results were validated through the gene expression analysis. Results from the present investigation suggest that piperine and thymol can be synergistically employed for the treatment of biofilm-associated C. albicans infection.
Highlights
The genus Candida is ubiquitously distributed and comprises more than 350 species of “yeast-like fungi” (Williams and Lewis, 2011; Williams et al, 2012)
The biofilm inhibitory potential of piperine against C. albicans was reported in our previous study (Priya and Pandian, 2020)
Piperine at 32 μg/ml inhibited the biofilm formation of the reference strain of C. albicans without affecting the viability (Figure 1A)
Summary
The genus Candida is ubiquitously distributed and comprises more than 350 species of “yeast-like fungi” (Williams and Lewis, 2011; Williams et al, 2012). The majority of the Candida species are unable to grow at 37°C and not generally associated with colonization of humans (Schauer and Hanschke, 1999) Certain species such as Candida albicans, C. glabrata, C. tropicalis, C. krusei, C. parapsilosis and C. dubliniensis exist as a part of the human commensal microbiota that can transmute to opportunistic pathogens under favourable conditions (Fisher et al, 1987; Vanden Abbeele et al, 2008; Luque et al, 2009; Martins et al, 2010; Meurman et al, 2011). C. albicans can directly interact either with the denture acrylic surface or with plaqueforming bacteria (Chandra et al, 2001)
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