Candida Biofilms: Threats, Challenges, and Promising Strategies

Abstract

Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

Keywords: Candida genus; antibiofilm strategies; antifungal resistance; biofilm formation; biofilm regulators; multi-species biofilm.

Figure 1

Comparative schematics the three stages of biofilm formation by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the different capacities to produce extracellular matrix (ECM), the varying components present in the ECM, and the ability to exhibit different cell morphologies.

Figure 2

Transcription regulatory network described for Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the transcriptional factors involved in adhesion, extracellular polymeric substances (EPS), filamentation, and biofilm. Green boxes indicate activators and red boxes indicate repressors. Participation of each transcription factor in these processes is indicated by the colored arrows: brown arrows correspond to adhesion, dark blue arrows correspond to EPS, light blue arrows correspond to filamentation, and yellow arrows correspond to biofilm formation.