biostudies-literaturePaing MMNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSBurroughs Wellcome FundNIAMS NIH HHSWellcome Truste43224https://www.ebi.ac.uk/biostudies/studies/S-EPMC6305201biostudies-literatureUnknown7Erythrocyte Binding Antigen of 175 kDa (EBA-175) has a well-defined role in binding to glycophorin A (GpA) during <i>Plasmodium falciparum</i> invasion of erythrocytes. However, EBA-175 is shed post invasion and a role for this shed protein has not been defined. We show that EBA-175 shed from parasites promotes clustering of RBCs, and EBA-175-dependent clusters occur in parasite culture. Region II of EBA-175 is sufficient for clustering RBCs in a GpA-dependent manner. These clusters are capable of forming under physiological flow conditions and across a range of concentrations. EBA-175-dependent RBC clustering provides daughter merozoites ready access to uninfected RBCs enhancing parasite growth. Clustering provides a general method to protect the invasion machinery from immune recognitioneLifeShed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion.PMC6305201R01 AI080792Extramural Research Program AI080792R01 AI137162P30 AR048335097945/B/11/ZIntramural Research ProgramR56 AI080792Jensen ATGoldberg DEOksman ATolia NHSalinas NDPaing MMAdams YfalseShed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion.Erythrocyte Binding Antigen of 175 kDa (EBA-175) has a well-defined role in binding to glycophorin A (GpA) during <i>Plasmodium falciparum</i> invasion of erythrocytes. However, EBA-175 is shed post invasion and a role for this shed protein has not been defined. We show that EBA-175 shed from parasites promotes clustering of RBCs, and EBA-175-dependent clusters occur in parasite culture. Region II of EBA-175 is sufficient for clustering RBCs in a GpA-dependent manner. These clusters are capable of forming under physiological flow conditions and across a range of concentrations. EBA-175-dependent RBC clustering provides daughter merozoites ready access to uninfected RBCs enhancing parasite growth. Clustering provides a general method to protect the invasion machinery from immune recognition2018-01-01T00:00:00Z2018 Dec2026-05-06T01:02:25.39Z2019-03-27T00:14:35ZS-EPMC63052013055680810.7554/eLife.43224