Control of Candida albicans morphology and pathogenicity by post-transcriptional mechanisms

Abstract

Candida albicans is a major human fungal pathogen responsible for both systemic and mucosal infections in a wide variety of immunocompromised individuals. Because the ability of C. albicans to undergo a reversible morphological transition from yeast to filaments is important for virulence, significant research efforts have focused on mechanisms that control this transition. While transcriptional and post-translational mechanisms have been well-studied, considerably less is known about the role of post-transcriptional mechanisms. However, in recent years several discoveries have begun to shed light on this important, but understudied, area. Here, I will review a variety of post-transcriptional mechanisms that have recently been shown to control C. albicans morphology, virulence and/or virulence-related processes, including those involving alternative transcript localization, mRNA stability and translation. I will also discuss the role that these mechanisms play in other pathogens as well as the potential they may hold to serve as targets for new antifungal strategies. Ultimately, gaining a better understanding of C. albicans post-transcriptional mechanisms will significantly improve our knowledge of how morphogenesis and virulence are controlled in fungal pathogens and open new avenues for the development of novel and more effective antifungals.

Candida parapsilosis: from Genes to the Bedside

“…To date, there is no record of true hyphae formed by C. parapsilosis. Environmental stimuli that are thought to influence morphology transition are stress-inducing conditions, including elevated temperature (37°C), the presence of serum, starvation, and high CO 2 levels and low O 2 levels that are present within the host (164)(165)(166). Although the exact inducers of the yeast-to-pseudohypha switch are poorly investigated, a specific subset of amino acids promotes this behavior (167).…”

Clinical strains of Lactobacillus reduce the filamentation of Candida albicans and protect Galleria mellonella against experimental candidiasis

“…The morphological transition from yeast to hyphal filaments occurs in response to a wide variety of conditions in the host environment. These conditions are reproducible in in vitro studies and include the presence of serum, body temperature (37°C), high CO 2 concentration, neutral pH, certain carbon sources or amino acids, and the extracellular matrix of microbial biofilms (de Kadosh 2016). The inhibition of these virulence factors in C. albicans is an important tool for the treatment of candidiasis.…”

The 5’ untranslated region of theEFG1transcript promotes its translation to regulate hyphal morphogenesis inCandida albicans

“…In eukaryotes, the level, processing, localization and/or structure of the primary transcript determine the initial amount of the encoded protein, which is subsequently lowered by different rates of proteolytic degradation. Some of such posttranscriptional processes and their underlying mechanisms have been described in C. albicans to regulate levels of proteins including transcription factors (15, 16). Transcript degradation involves poly(A) tail removal by deadenylase subunits Ccr4/Pop2 (17), hydrolysis of the 5’ cap by decapping activators Dhh1/Edc3 (18), decapping enzyme Dcp1 (18) and mRNA digestion by exonuclease Xrn1/Kem1 (19, 20).…”