Tamim El Jarkass Hala, Jeon JiHae, Burton Nicholas O, Reinke Aaron W
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, Michigan United States of America.
PLoS One. 2025 Jul 1;20(7):e0327188. doi: 10.1371/journal.pone.0327188. eCollection 2025.
Microsporidia are fungal-related obligate intracellular parasites that infect many types of animals. Microsporidia have exceptionally reduced genomes resulting in limited metabolic capabilities and are thought to be reliant on host metabolism to fuel their own growth. Here, we investigate the impact of microsporidia infection on host lipid metabolism using the nematode Caenorhabditis elegans along with its natural microsporidian pathogen Nematocida parisii. We show that infection causes an increase in the level of C. elegans lipid droplet associated lipase, ATGL-1, and a decrease in host fat levels. A mutation that decreases ATGL-1 activity and overexpression of ATGL-1 did not significantly change N. parisii infection levels. Using lipidomics we show that N. parisii infection decreases C. elegans triglyceride levels and results in increased ceramides that we speculate are synthesized by N. parisii. Mutations in host genes involved in ceramide synthesis did not significantly change the levels of N. parisii infection. Together these results show that microsporidia can cause changes to lipid metabolism of their hosts, but some individual mutations of C. elegans lipid enzymes do not alter microsporidian growth.
微孢子虫是与真菌相关的专性细胞内寄生虫,可感染多种动物。微孢子虫的基因组异常精简,导致其代谢能力有限,被认为依赖宿主代谢来为自身生长提供能量。在此,我们利用线虫秀丽隐杆线虫及其天然微孢子虫病原体巴黎嗜线虫致病杆菌,研究微孢子虫感染对宿主脂质代谢的影响。我们发现,感染会导致秀丽隐杆线虫脂质滴相关脂肪酶ATGL-1水平升高,宿主脂肪水平降低。降低ATGL-1活性的突变以及ATGL-1的过表达并未显著改变巴黎嗜线虫致病杆菌的感染水平。通过脂质组学分析,我们发现巴黎嗜线虫致病杆菌感染会降低秀丽隐杆线虫的甘油三酯水平,并导致神经酰胺增加,我们推测这些神经酰胺是由巴黎嗜线虫致病杆菌合成的。参与神经酰胺合成的宿主基因突变并未显著改变巴黎嗜线虫致病杆菌的感染水平。这些结果共同表明,微孢子虫可导致宿主脂质代谢发生变化,但秀丽隐杆线虫脂质酶的一些个别突变不会改变微孢子虫的生长。