Translational effect of farnesol on TUP1, a key regulator of morphological differentiation in the human fungal pathogen, Candida albicans.

Abstract

Candida albicans is an opportunistic polymorphic yeast that can cause life threatening systemic infections in immunocompromised individuals. It resides as commensal organism on the skin, in the gastrointestinal tracts and in the genitourinary tracts of mammalian hosts. One key attribute of C. albicans that enhances its pathogenicity is its ability to switch morphologies between unicellular yeast cells and filamentous forms, in response to diverse stimuli. C. albicansproduces farnesol as an extracellular autoregulatory compound and when farnesol accumulates above a threshold level, it inhibits yeast-to-hyphal switch as well as biofilm formation. It was shown that expression of the gene, TUP1 was slightly increased in response to farnesol, particularly at the transcriptional level and strains lacking the gene, did not respond to farnesol. To study the translational effect of farnesol on TUP1, a quantitative reverse transcriptase PCR (qRT-PCR) analysis was used to investigate the effect of farnesol on TUP1 mRNA across the polysome using RNA samples from input and polysome fractions of farnesol treated cells and cells not exposed to farnesol. The qRT-PCR data showed redistribution of the mRNA from the polysomal region to the sub-polysomal region following treatment with 100μM farnesol indicating an inhibition of the translation.