Farnesol signalling in Candida albicans – more than just communication

Abstract

Candida albicans is a successful colonizer of the human host, which can, under certain circumstances cause a range of clinically diverse infections. Important virulence-associated traits of the fungus, such as the dimorphic switch and biofilm formation, are controlled by the quorum sensing molecule farnesol. Given the potential of farnesol as a novel antifungal drug, there has been increasing research into the mechanism underlying farnesol sensing and action in C. albicans. However, despite the identification of various factors involved in farnesol signalling, its exact mode of action remains largely unclear. This review provides an overview of the currently known aspects of farnesol production, sensing and action within C. albicans. We also illustrate the characteristic of C. albicans to simultaneously produce and tolerate high farnesol concentrations that are lethal to other microbes. Furthermore, we summarize new literature on the role of farnesol in the interaction of C. albicans with the human host and highlight its action as a potent immunomodulatory molecule.

Effect of quorum sensing molecules and natamycin on biofilms of Candida tropicalis and other yeasts isolated from industrial juice filtration membranes

“…; Polke et al . ). Cells that were submitted to the pressure of both inhibitors, would hypothetically have experienced a blockade of protein transporters and inhibition of germ tube formation, together with an upregulation of metabolism.…”

“…Contrary to other antifungal agents like nystatin, it does not cause membrane permeabilization but rather inhibits glucose and amino acid protein transporters in the membrane by a steroldependent mechanism (te Welscher et al 2012). Farnesol inhibits germ tube formation and upregulates many metabolic pathways in C. albicans (Han et al 2012;Polke et al 2017). Cells that were submitted to the pressure of both inhibitors, would hypothetically have experienced a blockade of protein transporters and inhibition of germ tube formation, together with an upregulation of metabolism.…”

Fungi at the Scene of the Crime: Innocent Bystanders or Accomplices in Oral Infections?

“…Yet, interestingly, when at lower concentrations (25-50 μM) that are representative within these dualspecies biofilms, then it can stimulate S. mutans microcolony development and enhance biofilm formation [67]. It is therefore thought that this is a key maintenance molecule with regard to regulating microbial fitness and biofilm formation in oral plaque [68]. If indeed candidal yeasts are important physical and metabolic members of cariogenic microbiomes, then this may explain why S. mutans centric therapeutic approaches have failed.…”

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

“…T he proliferation and virulence of Candida cells are under strict cell density-based control mediated by various quorum-sensing molecules, including farnesol and tyrosol (1,2). While farnesol induces the hypha-to-yeast transition in Candida albicans, tyrosol has an opposite effect.…”

“…In recent years, alternative treatments targeting quorum sensing against Candida species have become an intensively researched area; however, tyrosol remains a mysterious molecule, and the exact background of its antifungal mechanism is still poorly understood (1,2,(8)(9)(10). In the case of C. albicans, both the transcriptional and physiological responses exerted by tyrosol have been addressed previously (3,4), aiding in the understanding of the observed antifungal effect against C. albicans.…”