Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update

Abstract

Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.

Candida albicans biofilms and polymicrobial interactions

“…In addition to the Als family, other adhesins are important in mediating the initial attachment of C. albicans yeast cells during biofilm formation (Figure 1(A)). The enhanced adhesion to polystyrene protein (Eap1p) is significant in the clinical setting due to its ability to mediate attachment of C. albicans to plastics found in medical devices (Chong et al 2018;McCall et al 2019). Deletion of EAP1 renders C. albicans unable to attach to plastic surfaces and epithelial cells in vitro.…”

Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection

“…Biofilms are organized communities of cells developed after adhesion to a surface and enclosed in an ECM [107, 108]. The ability to grow as biofilms presents an advantage for fungal pathogens, regarding colonization and persistence in different host tissues [109], but also in the resilience against antifungal treatments [110, 111].…”

Sodium New Houttuyfonate Inhibits Candida albicans Biofilm Formation by Inhibiting the Ras1-cAMP-Efg1 Pathway Revealed by RNA-seq

“…With the development of genomics and the advent of whole genome sequencing platforms, metabolic pathways and related genes involved in fungal pathogenesis have been revealed ( Chong et al, 2018 ). The current study found that the anti-adhesive effects of SNH are more significant than its anti-biofilm effects, and to verify that SNH may inhibit biofilm formation by inhibiting initial adhesion, we sequenced the transcriptome of C. albicans at an initial adhesion phase in 256 μg/mL (1 MIC 80 ) SNH treatment and control groups through a high-throughput RNA sequencing method.…”