Abstract
Candida albicans is the primary etiological agent associated with the pathogenesis of candidiasis. Unrestricted growth of C. albicans in the oral cavity may lead to oral candidiasis, which can progress to systemic infections in worst scenarios. Biofilm of C. albicans encompasses yeast and hyphal forms, where hyphal formation and yeast to hyphal morphological transitions are contemplated as the key virulence elements. Current clinical repercussions necessitate the identification of therapeutic agent that can limit the biofilm formation and escalating the susceptibility of C. albicans to immune system and conventional antifungals. In the present study, a plant-derived alkaloid molecule, piperine, was investigated for the antibiofilm and antihyphal activities against C. albicans. Piperine demonstrated a concentration-dependent antibiofilm activity without exerting negative impact on growth and metabolic activity. Inhibition in the hyphal development was witnessed through confocal laser-scanning microscopy and scanning electron microscopy. Interestingly, piperine displayed a tremendous potential to inhibit the virulence-associated colony morphologies, such as filamentation and wrinkling. Furthermore, piperine regulated morphological transitions between yeast and hyphal forms by inhibiting hyphal extension and swapping hyphal phase to yeast forms yet under filamentation-inducing circumstances. Remarkably, piperine-challenged C. albicans exhibited low potential for spontaneous antibiofilm resistance development. In addition, piperine effectively reduced in vivo colonization and prolonged survival of C. albicans-infected Caenorhabditis elegans, thereby expounding the distinct antivirulent potential. Transcriptomic analysis revealed piperine significantly downregulating the expression of several biofilm related and hyphal-specific genes (ALS3, HWP1, EFG1, CPH1, etc.). Furthermore, no acute toxicity was observed in the HBECs and nematodes exposed to piperine. Altogether, results from this study reveals the potential of piperine to inhibit biofilm and hyphal morphogenesis, and its in vivo efficacy and innocuous nature to HBECs suggests that piperine may be considered as a potential candidate for the treatment of biofilm-associated C. albicans infection, especially for oral candidiasis.
Highlights
Members of Candida spp. are commensal inhabitants in human microbiota, which expediate their encounter with host surfaces, such as mucosal linings and abiotic prosthetic biomaterials (Ramage et al, 2005)
Amid the diverse fungal species, C. albicans stands as the predominant organism associated with the biofilm formation, which is one of the major virulence traits devoted to its versatile pathogenicity
In order to attenuate the biofilm formation and virulence traits of C. albicans, with decreased avenue for resistance development, this study demonstrated the use of a plant alkaloid, piperine, as an effective antibiofilm and antihyphal molecule against C. albicans biofilm infection
Summary
Members of Candida spp. are commensal inhabitants in human microbiota, which expediate their encounter with host surfaces, such as mucosal linings and abiotic prosthetic biomaterials (Ramage et al, 2005). Undesirable predisposing circumstances such as extremes in age, diminished immune system, diabetes mellitus, HIV/AIDS, and exploitation of broadspectrum antibiotics pave way for Candida spp. to mount pathogenicity that trails to candidiasis progressively (Akpan and Morgan, 2002; Millsop and Fazel, 2016). When any of these barriers are subsided, overgrowth of C. albicans can lead to mild local discomfort and altered taste sensation to severe systemic infections with significant morbidity and mortality (Rajendran et al, 2016)
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