Cutaneous mycotic infections are becoming increasingly difficult to manage owing to a plethora of factors, an important one being the gradual but steadily increasing development of resistance in the causative fungal species against multiple standard antifungal drugs. Onychomycosis (ONM) presents a peculiar situation where despite retained drug susceptibility by the causative fungus, the effect of antifungal drugs is suboptimal. Although genetically determined anergy, or lack of immune response to specific fungal antigens, have been reported in patients with chronic dermatophytosis (e.g., ONM is often ignored by the affected patients for years before seeking treatment), factors such as pathogen virulence, drug resistance, and most importantly formation of biofilms by and Candida spp. contribute to the suboptimal or nonresponse to drugs in ONM [ ]. Microbial pathogens including fungi have become smarter and more civilized by secreting a thick layer of extracellular polymeric substance composed of polysaccharides, proteins, lipids, and extracellular DNA, which constitute the biofilm within which they thrive and survive, supporting each other in a colonial fashion. In addition to the formation of a robust impenetrable mechanical barrier that insulates their colonies from the environment (especially topical antifungals), biofilms provide increased communication, virulence, better metabolic cooperation, and concerted gene expression, leading to increased resistance to antifungal agents (for example, by activation of drug efflux pump genes). Moreover, the host immune system is unable to access the fungi encased in a mature biofilm, leading to tissue damage from an ineffectual immune response with persistence of infection [ , ]. Therefore, disruption of fungal biofilms before or concomitant with antifungal drug therapy is essential for successful eradication of infection. The biofilm can be tackled at three steps of its formation and maturation. Fungal biofilms have a complex three-dimensional structure and diverse spatial heterogeneity. Typically, biofilms are embedded in an extracellular matrix encased within exopolymeric material with a microcolony/water channel architecture.
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