Protection against Babesia infection by red blood cell PIEZO1 activation

Babesia divergens are tick-borne apicomplexan parasites infecting red blood cells of domestic and wild animals in Europe, as well as humans with important health burden. Previous findings indicate that PIEZO1 gain-of-function inherited mutations confer a significant protection against cerebral malaria. In this study, we further demonstrate that several Yoda1 analogs promoting PIEZO1 opening prevent B. divergens infection of human red blood cells in vitro. We identify several compounds with improved specificity for B. divergens, as compared to Plasmodium falciparum.

Babesia are apicomplexan parasites transmitted by tick bites that mainly infect animals, but some species such as Babesia divergens also infect people with dramatic outcomes. Babesiosis represents a threat for bovine production and is also an emerging human infectious disease in endemic regions. Like the malaria parasite Plasmodium, Babesia infects red blood cells (RBC) and causes hemolysis. Protection is currently based on drug treatments, tick control strategies, and animal vaccination. However, the indiscriminate use of prophylactic agents directly targeting the parasite is at risk to cause drug resistance, as observed for malaria. Here, we show that PIEZO1 activation in human RBC, taking advantage of newly synthesized Yoda1 analogs with enhanced efficacy and lower cytotoxicity, confers in vitro protection against Babesia infection.