Glycerophosphocholine provision rescues Candida albicans growth and signaling phenotypes associated with phosphate limitation.
Glycerophosphocholine provision rescues Candida albicans growth and signaling phenotypes associated with phosphate limitation.
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真菌病原体白色念珠菌必须获得磷酸盐才能在人类宿主中定殖、感染和增殖。C.白色念珠菌有四种无机磷酸盐（Pi）转运蛋白，Pho 84是主要的高亲和力转运蛋白;其细胞也可以使用甘油磷酸胆碱（GPC）作为其唯一的磷酸盐来源。GPC是由脂质磷脂酰胆碱脱酰化衍生的脂质代谢物。GPC存在于多种人体组织中，包括肾髓质，在那里它充当渗透剂。C.白色念珠菌通过Git 3和Git 4转运蛋白将GPC输入细胞。内化的GPC可以水解以释放Pi。为了确定GPC输入和随后的代谢是否影响Pi限制后的磷酸盐稳态，我们监测了提供有Pi或GPC的细胞中的生长和表型输出。在表现出与Pi限制相关的表型的pho 84 α/β突变细胞中，GPC提供拯救了对渗透压和细胞壁应力的敏感性。甘油磷酸二酯酶Gde 1是GPC提供的渗透胁迫表型救援所需的。GPC规定，如Pi规定，导致抑制PHO调节子和TORC 1信号转导的激活。当磷酸盐可用性较低（200 µM）时，Pi吸收与GPC吸收相似。虽然GPC在人类宿主中的浓度低于Pi，但GPC是真菌的有利Pi来源，因为它同时充当胆碱来源。总之，我们发现GPC能够取代C中的Pi。白念珠菌的许多标准，但不是所有的标准，并可能有助于磷酸盐的真菌在人类宿主。白色念珠菌是最常见的从患有侵袭性真菌疾病的患者分离的菌种。C.白色念珠菌是最常见的一种寄生在人体宿主各种小生境中的微生物。真菌必须与宿主植物群竞争资源，以获得必需的营养物质，如磷酸盐。磷酸盐的获得和体内平衡已被证明在C.白念珠菌的毒力，与参与这些过程的几个基因所需的正常毒力和几个在感染过程中上调。除无机磷（Pi）外，C.白色念珠菌可以利用脂质衍生的代谢物甘油磷酸胆碱（GPC）作为磷酸盐来源。由于GPC在人类宿主中可用，我们研究了GPC在C中磷酸盐稳态中的作用。白色念珠菌我们发现GPC可以通过许多但不是所有的标准替代Pi，并且可能是C的相关生理磷酸盐来源。白色念珠菌
The fungal pathogen Candida albicans must acquire phosphate to colonize, infect, and proliferate in the human host. C. albicans has four inorganic phosphate (Pi) transporters, Pho84 being the major high-affinity transporter; its cells can also use glycerophosphocholine (GPC) as their sole phosphate source. GPC is a lipid metabolite derived from deacylation of the lipid phosphatidylcholine. GPC is found in multiple human tissues, including the renal medulla, where it acts as an osmolyte. C. albicans imports GPC into the cell via the Git3 and Git4 transporters. Internalized GPC can be hydrolyzed to release Pi. To determine if GPC import and subsequent metabolism affect phosphate homeostasis upon Pi limitation, we monitored growth and phenotypic outputs in cells provided with either Pi or GPC. In pho84∆/∆ mutant cells that exhibit phenotypes associated with Pi limitation, GPC provision rescued sensitivity to osmotic and cell wall stresses. The glycerophosphodiesterase Gde1 was required for phenotypic rescue of osmotic stress by GPC provision. GPC provision, like Pi provision, resulted in repression of the PHO regulon and activation of TORC1 signaling. Pi uptake was similar to GPC uptake when phosphate availability was low (200 µM). While available at lower concentrations than Pi in the human host, GPC is an advantageous Pi source for the fungus because it simultaneously serves as a choline source. In summary, we find GPC is capable of substituting for Pi in C. albicans by many though not all criteria and may contribute to phosphate availability for the fungus in the human host. Candida albicans is the most commonly isolated species from patients suffering from invasive fungal disease. C. albicans is most commonly a commensal organism colonizing a variety of niches in the human host. The fungus must compete for resources with the host flora to acquire essential nutrients such as phosphate. Phosphate acquisition and homeostasis have been shown to play a key role in C. albicans virulence, with several genes involved in these processes being required for normal virulence and several being upregulated during infection. In addition to inorganic phosphate (Pi), C. albicans can utilize the lipid-derived metabolite glycerophosphocholine (GPC) as a phosphate source. As GPC is available within the human host, we examined the role of GPC in phosphate homeostasis in C. albicans. We find that GPC can substitute for Pi by many though not all criteria and is likely a relevant physiological phosphate source for C. albicans.
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3.3
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