Fungal Biofilm - A Real Obstacle against an Efficient Therapy: Lessons from Candida.

The past decades have witnessed a dramatic increase in invasive fungal infections, especially caused by different species belonging to the Candida genus. Nowadays, even after many improvements in several medical procedures, Candida infections (candidiasis) still account for an unacceptable high rate of morbimortality in hospital settings. Corroborating this statement, fungal biofilms formed on both abiotic and living surfaces are responsible for an important medical and economic burden, since biofilm lifestyle confers numerous advantages to the pathogens, including high tolerance to environmental stresses such as antimicrobials and host immune responses. Aggravating this scenario, the currently used antifungal drugs have mostly been developed to target exponentially growing fungal cells and are poorly or not effective against biofilm structures. So, the challenges to inhibit biofilm formation (e.g., blocking the fungal adhesion and its fully development due to the changes of physicochemical properties of the inert substrates by covering or impregnating them with antimicrobial compounds, for example, silver nanoparticles) and/or to disarticulate mature biofilm architecture (e.g., by using compounds capable in destabilizing, weakening or destroying the extracellular matrix components, including inhibitors of quorum sensing signals, hydrolytic enzymes, surfactants, chelator agents and biocides) are stimulating researchers around the world to search novel strategies and new chemotherapeutic options to control fungal biofilm. In this context, the present review summarizes some promising approaches and/or strategies that could improve our ability to prevent or eradicate fungal biofilms in medical settings, focusing on the lessons learned with Candida model.