True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus

Here, we reveal that T. foetus produces true cysts characterized by chitin like components-rich, fibrillar walls, cytoskeletal reorganization, and resistance to detergent treatment. Cystogenesis is induced by environmental stresses such as nutrient deprivation, alkaline pH mimicking the bovine preputial milieu, and exposure to metronidazole, a frontline antiparasitic drug.

This encystation enhances parasite survival and suggests a novel drug-resistance mechanism. Transcriptomic profiling identifies key pathways involved in cyst wall biosynthesis and regulation, including Myb-like transcription factors and calcium/calmodulin dependent kinases. Encysted parasites also undergo DNA replication without cytokinesis, suggesting a strategy for rapid multiplication through multiple fission upon excystation.