Abstract
The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular molecules, whose concentration is proportional with cell density. Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) have a pivotal role in morphogenesis, biofilm formation, and virulence. Farnesol can mediate the hyphae-to-yeast transition, while tyrosol has the opposite effect of inducing transition from the yeast to hyphal form. A number of questions regarding Candida quorum sensing remain to be addressed; nevertheless, the literature shows that farnesol and tyrosol possess remarkable antifungal and anti-biofilm effect at supraphysiological concentration. Furthermore, previous in vitro and in vivo data suggest that they may have a potent adjuvant effect in combination with certain traditional antifungal agents. This review discusses the most promising farnesol- and tyrosol-based in vitro and in vivo results, which may be a foundation for future development of novel therapeutic strategies to combat Candida biofilms.
Highlights
It has been estimated that there are 2.2 to 3.8 million fungal species worldwide; approximately 300 species have been described to cause human disease [1]
A major mechanism of microbial communication is a population density-dependent stimulus-response system called quorum sensing. This process occurs by the continuous release and monitoring of low molecular weight hormone-like secreted molecules, which are not elementary in the central metabolism but have a variety of biological activities. The concentration of these quorum-sensing molecules is proportional with the size of population; after reaching a critical threshold, a response is triggered leading to the coordinated expression or repression of quorum sensing-related target genes [37]
Farnesol (3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) was the first described Candida-derived quorum sensing molecule; it is released in C. albicans as a side product of the sterol synthetic pathway by dephosphorylation of farnesol pyrophosphate [38,46]
Summary
It has been estimated that there are 2.2 to 3.8 million fungal species worldwide; approximately 300 species have been described to cause human disease [1]. Global warming and anthropogenic effects have resulted in the emergence of previously little-known, potentially multi-resistant fungal pathogens in clinical practice, such as Candida auris, azole-resistant Aspergillus spp., or Lomentospora prolificans. These emerging pathogens have caused further challenges for therapy [6,7]. The increased number of biofilm-associated infections is exacerbated by a paucity of antifungal agents or therapeutic strategies in development that have unique mechanisms of action or possess alternative approaches, respectively [11]. A detailed overview is provided of the recent status of quorum-sensing molecule-based therapeutic approaches and their potential future perspectives against Candida biofilms
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