Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
J Microbiol Immunol Infect. 2020 Feb;53(1):115-124. doi: 10.1016/j.jmii.2018.04.002. Epub 2018 May 17.
Candida albicans is an opportunistic pathogen capable of causing life-threatening systemic infections. The C. albicans ARO1 gene encodes an arom multifunctional enzyme, which can possibly catalyze reactions of the shikimate pathway to synthesize aromatic amino acids. However, the functions of C. albicans Aro1 have not been extensively characterized.
ARO1 knockdown mutant strain was constructed, using a tetracycline-regulated (TR) expression system. Cell growth of the mutant strain was compared with wild type. Effects of the ARO1 gene knockdown on cell wall properties, adhesion to polystyrene and biofilm formation were further investigated. Finally, Galleria mellonella was used as a model host to study the role of ARO1 in virulence of C. albicans.
We showed that defective growth in the ARO1 knockdown strain was rescued by supplemental aromatic amino acids. In addition, the ARO1 knockdown strain was easily aggregated and precipitated. The knockdown of ARO1 also caused changes in cell wall properties and compositions and promoted C. albicans cell adhesion to polystyrene and biofilm formation. Finally, the ARO1 knockdown strain showed attenuation of C. albicans virulence.
This work provides new insights into C. albicans metabolism, cell wall and virulence.
白色念珠菌是一种机会致病菌，能够导致危及生命的全身感染。白色念珠菌 ARO1 基因编码一种芳香族多功能酶，可能催化莽草酸途径的反应，合成芳香族氨基酸。然而，白色念珠菌 Aro1 的功能尚未得到广泛表征。
使用四环素调控（TR）表达系统构建 ARO1 敲低突变株。比较突变株和野生型的细胞生长情况。进一步研究 ARO1 基因敲低对细胞壁特性、对聚苯乙烯的黏附以及生物膜形成的影响。最后，使用家蚕作为模型宿主研究 ARO1 在白色念珠菌毒力中的作用。
我们表明，在 ARO1 敲低菌株中，补充芳香族氨基酸可以挽救其生长缺陷。此外，ARO1 敲低菌株容易聚集和沉淀。ARO1 的敲低还导致细胞壁特性和组成发生变化，并促进白色念珠菌细胞对聚苯乙烯的黏附以及生物膜的形成。最后，ARO1 敲低菌株表现出白色念珠菌毒力的减弱。
这项工作为白色念珠菌代谢、细胞壁和毒力提供了新的见解。
