Liu Rong, Cheng Wen-Jun, Tang Hong-Bin, Zhong Qin-Ping, Ming Zhen-Ping, Dong Hui-Fen
School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Front Microbiol. 2019 Mar 12;10:440. doi: 10.3389/fmicb.2019.00440. eCollection 2019.
The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches.
血吸虫的生长和发育在免疫缺陷宿主中受到了影响。但是，关于参与血吸虫发育和繁殖调控的分子机制仍未得到解决。本研究使用液相色谱串联质谱（LC-MS/MS）平台，检测并比较了感染后5周从SCID小鼠和BALB/c小鼠体内收集的雄虫和雌虫的代谢谱，其中以SCID小鼠体内的虫体作为研究对象，BALB/c小鼠体内的虫体作为对照。经错误发现率过滤后，在ESI+模式下鉴定出1015个离子特征峰，在ESI-模式下鉴定出342个离子特征峰。使用主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）等多变量建模方法，发现明显的代谢谱能够清晰地区分SCID小鼠体内的雄虫和雌虫与BALB/c小鼠体内的雄虫和雌虫。在SCID小鼠和BALB/c小鼠之间，雌虫中的差异代谢物比雄虫中的更多。与BALB/c小鼠相比，还鉴定出了SCID小鼠雄虫和雌虫中共同和独特的受干扰代谢物及代谢途径。SCID小鼠和BALB/c小鼠雄虫中差异代谢物的富集代谢物集包括胆汁酸生物合成、牛磺酸和亚牛磺酸代谢、鞘脂代谢、视黄醇代谢、嘌呤代谢等。雌虫中差异代谢物的富集代谢物集包括视黄醇代谢、α-亚麻酸和亚油酸代谢、嘌呤代谢、鞘脂代谢、谷氨酸代谢等。对受干扰的视黄醇代谢及其在虫体中相关减数分裂过程的基因转录丰度进行进一步检测和比较，发现了提示视黄酯积累和减数分裂过程受干扰的线索。这些发现表明，SCID小鼠体内生长发育迟缓的血吸虫与其受干扰的代谢物和代谢途径之间存在关联，并从代谢水平为蠕虫的生长发育调控提供了新的见解，这为进一步研究发现抗寄生虫和疾病的药物或疫苗提供了重要线索。
