Loss of vitamin C biosynthesis protects from the pathology of a parasitic infection
Abstract
The ability to synthesize essential molecules is sometimes lost in evolution. A classic example is ascorbate (vitamin C), which is synthesized in most animals by L-gulonolactone oxidase (GULO), an enzyme lost multiple independent times in animal evolution. This event is thought to be evolutionarily neutral; however, GULO- deficient animals including humans need to obtain ascorbate from their diet and are prone to ascorbate deficiency and scurvy. We therefore hypothesized that this disadvantage of GULO loss is offset by physiological benefits. Here, we show that ascorbate deficiency benefits mice infected with schistosome parasites, which cause schistosomiasis, a debilitating parasitic disease that afflicts 250 million people. Schistosoma mansoni worms required host ascorbate to produce eggs in vivo. Consequently, ascorbate-deficient mice were protected from schistosomiasis pathologies and transmission. Intermittent ascorbate deficiency protected Gulo -deficient mice from both scurvy and schistosomiasis mortality. The effects of ascorbate on schistosome reproduction were mediated by ascorbate-dependent histone demethylation which promoted vitellocyte development in female schistosomes. We propose that vitamin deficiencies are not always detrimental but can protect animals from pathogens which need to obtain vitamins from their host.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Gongwen Chen
State Key Laboratory of Genetics and Development of Complex Phenotypes, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Microbiology and Immunology, School of Life Sciences, Fudan University
Ji Hyung Jun
Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tobias Wijshake
Children’s Medical Center Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center
Edward O. Kwarteng
Children’s Medical Center Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center
Yunyang Li
State Key Laboratory of Genetics and Development of Complex Phenotypes, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Microbiology and Immunology, School of Life Sciences, Fudan University
Minwei Yuan
State Key Laboratory of Genetics and Development of Complex Phenotypes, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Microbiology and Immunology, School of Life Sciences, Fudan University
Joseph Rose
Children’s Medical Center Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center
Shan Li
Institute of Solid State Chemistry, Department of Physical Chemistry, Beijing Advanced Innovation Center for Materials Genome Engineering
Sarah Cobb
Department of Pharmacology, University of Texas Southwestern Medical Center
Willow Serpa
Department of Pharmacology, University of Texas Southwestern Medical Center
Brayden Folger
Department of Pharmacology, University of Texas Southwestern Medical Center
Yafeng Li
Children’s Medical Center Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center
Li Li
Weina Chen
Department of Pathology, University of Texas Southwestern Medical Center
James J. Collins
Department of Pharmacology, University of Texas Southwestern Medical Center
Jipeng Wang
State Key Laboratory of Genetics and Development of Complex Phenotypes, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Microbiology and Immunology, School of Life Sciences, Fudan University
Michalis Agathocleous
Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.