Small molecule based anti-virulence approaches against Candida albicans infections.

Fungi are considered "silent killers" due to the difficulty of, and delays in diagnosis of infections and lack of effective antifungals. This challenge is compounded by the fact that being eukaryotes, fungi share several similarities with human cellular targets, creating obstacles to drug discovery. Candida albicans, a ubiquitous microbe in the human body is well-known for its role as an opportunistic pathogen in immunosuppressed people. Significantly, C. albicans is resistant to all the three classes of antifungals that are currently clinically available. Over the past few years, a paradigm shift has been recommended in the management of C. albicans infections, wherein anti-virulence strategies are considered an alternative to the discovery of new antimycotics. Small molecules, with a molecular weight <900 Daltons, can easily permeate the cell membrane and modulate the signal transduction pathways to elicit desired virulence inhibitory actions against pathogens. This review dissects in-depth, the discoveries that have been made with small-molecule anti-virulence approaches to tackle C. albicans infections.

Interactions between Candida albicans and Enterococcus faecalis in an Organotypic Oral Epithelial Model.

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.