A Nonribosomal Peptide Pheromone Controls Male-Induced Female Sexual Development in Schistosoma mansoni
Schistosomes are parasites causing one of most prevalent and serious neglected tropical diseases. Their immense egg output in the host is the main source of pathology, placing their reproductive biology of great importance for scientific researches. A bizarre, and physiologically meaningful phenomenon of their reproduction process is that a female schistosome requires constant physical pairing by the male worms to achieve sexual maturity for egg production. The stimulation of the pairing is even sufficient to induce parthenogenetic eggs from the females when insemination is artificially ablated. The molecular mechanism of the process is unknown despite the attention of 100 years. In this study, a master transcription regulator (GLI1), a nonribosomal peptide synthetase (SmNRPS) and a pheromone metabolite β-alanyl-tryptamine (BATT) were discovered to firstly demonstrate the way a male parasite might signal his paired female. Using RNA sequencing, biochemistry assays and metabolomic analysis, we believe a male parasite starts to secret SmNRPS synthesized BATT into his pairing groove, upon copulation, to stimulate the paired female. The process is activated through transcription upregulation of the enzyme by GLI1. Virgin female Schistosoma mansoni can sexually develop and eventually lay eggs by being soaked in BATT supplemented media. This result is pioneering in understanding the schistosome female-male interplay and provides novel therapeutic targets directly related to schistosomiasis pathology.
Parasites, Peptides, Pheromones, Schistosoma mansoni, Cell Culture Techniques
University of Texas Southwestern Medical Center
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