Physiological adventures in Candida albicans : farnesol and ubiquinones

法尼醇 生物 白色念珠菌 细胞生物学 酵母 微生物学 焦磷酸法尼酯 细胞内 群体感应 生物化学 毒力 生物合成 基因
作者
Kenneth W. Nickerson,Daniel J. Gutzmann,Cory H. T. Boone,Ruvini U. Pathirana,Audrey L. Atkin
出处
期刊:Microbiology and Molecular Biology Reviews [American Society for Microbiology]
卷期号:88 (1) 被引量:6
标识
DOI:10.1128/mmbr.00081-22
摘要

SUMMARY Farnesol was first identified as a quorum-sensing molecule, which blocked the yeast to hyphal transition in Candida albicans , 22 years ago. However, its interactions with Candida biology are surprisingly complex. Exogenous (secreted or supplied) farnesol can also act as a virulence factor during pathogenesis and as a fungicidal agent triggering apoptosis in other competing fungi. Farnesol synthesis is turned off both during anaerobic growth and in opaque cells. Distinctly different cellular responses are observed as exogenous farnesol levels are increased from 0.1 to 100 µM. Reported changes include altered morphology, stress response, pathogenicity, antibiotic sensitivity/resistance, and even cell lysis. Throughout, there has been a dearth of mechanisms associated with these observations, in part due to the absence of accurate measurement of intracellular farnesol levels ( F i ). This obstacle has recently been overcome, and the above phenomena can now be viewed in terms of changing F i levels and the percentage of farnesol secreted. Critically, two aspects of isoprenoid metabolism present in higher organisms are absent in C. albicans and likely in other yeasts. These are pathways for farnesol salvage (converting farnesol to farnesyl pyrophosphate) and farnesylcysteine cleavage, a necessary step in the turnover of farnesylated proteins. Together, these developments suggest a unifying model, whereby high, threshold levels of F i regulate which target proteins are farnesylated or the extent to which they are farnesylated. Thus, we suggest that the diversity of cellular responses to farnesol reflects the diversity of the proteins that are or are not farnesylated.
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