FarnesoI beyond morphogenesis controI: effect in Non- Candida albicans Candida species

Abstract

Candididasis is one of the most important life-tbreatening opportunistic mycosis mainly occurring in individuais with impaired immunity. Although Candida albicans remains the most common fungai isolate, an increase in Non-Candida albicans Candida (NCAC) species is being reported. ln fact, Candida glabrata, Candida krusei, Candida parapsilosis and Candida tropicalis are emerging as clinically relevant pathogens. So it is of great importance to study the mechanisms of infection by these new species. Recently, farnesol, a quorum sensing molecule in Candida albicans has been the focus of intense study conceming its effect in Candida's virulence and consequently its potential application as therapeutic agent. Nevertheless, to date, the action and role of famesol within Candida genus is yet not known. ln this sense, the aim of this study is to gain insights into the effect of famesol in NCAC species. Accordingly, the effect of famesol on Candida glabrata, Candida krusei, Candida parapsilosis and Candida tropicalis reference strains morphology and growth was evaluated. To assess morphological alterations, cells were grown ovemight in RPMI medium supplemented with 150 micromolar famesol and inspected under contrast light microscopy, after ovemight growth. Candida species famesol susceptibilities were assayed at 0.5, 5, 50, 100 and 150 micromolar. Growth medium, famesoI solutions and inocula were prepared following the recommendations outlined by the National Committee for Clinical Laboratory Standards M-27A adapted to micro-dilution. The obtained results show that, at the concentrations assayed, famesol has an antifungal activity against NCAC species, with different susceptibility profiles. Additionally, surviving cells exposed to the highest famesol concentrations did not present morphological alterations comparing to controls. These findings show that the quorum sensing molecule, famesol, has distinct species-specific effects, different from those described for Candida albicans. Moreover, the results presented herein suggest that famesol may play a pivotal role in inter-species growth control, namely within mixed Candida species cultures by the regulation ofdifferent cellular processes.