Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum.
Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum.
复制标题
磷酸葡萄糖转运和利用的多种途径支持小隐孢子虫的生长。
DOI：
10.1101/2023.06.27.546703
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Sibley,LDavid
中科院分区：
文献类型：
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作者：
Xu,Rui;Beatty,WandyL;Greigert,Valentin;Witola,WilliamH;Sibley,LDavid
隐孢子虫是一种专性细胞内寄生虫，具有高度还原的线粒体，缺乏三羧酸循环和产生ATP的能力，使寄生虫依赖于糖酵解。基因消融实验表明，两个假定的葡萄糖转运蛋白CpGT 1和CpGT 2都不是生长所必需的。令人惊讶的是，己糖激酶也是寄生虫生长所必需的，而下游酶醛缩酶是必需的，这表明寄生虫具有获得磷酸化己糖的替代方式。在E.大肠杆菌支持通过寄生虫转运蛋白CpGT 1和CpGT 2从宿主细胞直接转运葡萄糖-6-磷酸的作用，从而绕过对己糖激酶的需求。此外，寄生虫从支链淀粉库获得磷酸化葡萄糖，支链淀粉库通过必需酶糖原磷酸化酶的作用释放。总的来说，这些发现表明C. Parvum依赖于多种途径来获得磷酸化葡萄糖，用于糖酵解和恢复碳水化合物储备。
Cryptosporidium parvumis an obligate intracellular parasite with a highly reduced mitochondrion that lacks the tricarboxylic acid cycle and the ability to generate ATP, making the parasite reliant on glycolysis. Genetic ablation experiments demonstrated that neither of the two putative glucose transporters CpGT1 and CpGT2 were essential for growth. Surprisingly, hexokinase was also dispensable for parasite growth while the downstream enzyme aldolase was required, suggesting the parasite has an alternative way of obtaining phosphorylated hexose. Complementation studies inE. colisupport a role for direct transport of glucose-6-phosphate from the host cell by the parasite transporters CpGT1 and CpGT2, thus bypassing a requirement for hexokinase. Additionally, the parasite obtains phosphorylated glucose from amylopectin stores that are released by the action of the essential enzyme glycogen phosphorylase. Collectively, these findings reveal thatC. parvumrelies on multiple pathways to obtain phosphorylated glucose both for glycolysis and to restore carbohydrate reserves.