Recently, Professor Xiao Lihua and his team from the New Emerging and Zoonotic Disease Research Center at South China Agricultural University, along with collaborators, achieved a significant breakthrough in the study of the ribose metabolism of Toxoplasma gondii, a pathogen causing zoonotic diseases. Their research unveiled the metabolic adaptation mechanisms of Toxoplasma gondii in adapting to parasitic life. The findings have been published online in Nature Communications.
Toxoplasma gondii reprograms its ribose-5-phosphate metabolism under genetic perturbation. Image courtesy of the research team.
Toxoplasma gondii is a significant foodborne pathogen that often causes miscarriages and stillbirths in humans and animals, posing a serious threat to human health and livestock farming. There are currently no ideal drugs or vaccines available. Therefore, deciphering the parasite's parasitic mechanism, especially its important metabolic pathways, could provide targets for drug and vaccine design.
This study focused on the metabolism of ribose-5-phosphate, an important precursor for DNA synthesis in T. gondii. Through gene editing, cell and animal models, metabolic flux tracing, and other methods, the study revealed a network of ribose-5-phosphate metabolism consisting of multiple pathways. It elucidated the roles of these pathways in parasite growth and pathogenesis, demonstrating that when one metabolic pathway is disrupted, the parasite reprograms its ribose-5-phosphate metabolism. This explains T. gondii's adaptive mechanism in unfavorable environments.
Further research found that 5'-phosphoribosylpyrophosphate synthase, a downstream enzyme in the metabolic pathway, is essential for parasite growth and development, making it a promising target for drug development. The study also uncovered the molecular mechanism by which transketolase affects parasite growth and pathogenesis. It discovered that strains with ribose metabolism defects have the potential to become attenuated live vaccines.
This research was supported by the Major Program of Basic and Applied Basic Research of Guangdong Province, the National Natural Science Foundation of China, and the Research Projects of the Guangdong Provincial Key Laboratory of Lingnan Modern Agriculture Science and Technology, among others. Associate Professor Xia Ningbo, Professor Feng Yaoyu from the College of Veterinary Medicine of South China Agricultural University, and Professor Nishith Gupta from Humboldt University of Germany are the corresponding authors of the paper. Graduate students Guo Xuefang and Ji Nuo from the College of Veterinary Medicine of South China Agricultural University are the co-first authors of the paper.
For more information, see: https://doi.org/10.1038/s41467-024-47097-8
