title: A role for the Plasmodium falciparum RESA protein in resistance against heat shock demonstrated using gene disruption.
abstract: During erythrocyte invasion, the Plasmodium falciparum Ring-infected erythrocyte surface antigen (RESA) establishes specific interactions with spectrin. Based on analysis of strains with a large chromosome 1 deletion, RESA has been assigned several functions, none of which is firmly established. Analysis of parasites with a disrupted resa1 gene and isogenic parental or resa3-disrupted controls confirmed the critical role of RESA in the surface reactivity of immune adult sera on glutaraldehyde-fixed ring stages. Absence of RESA did not influence merozoite invasion or erythrocyte membrane rigidity, was associated with a modest increase of cytoadhesion to CD36 under conditions of flow, but resulted in marked susceptibility to heat shock. resa1-KO-infected erythrocytes were prone to heat-induced vesiculation like uninfected erythrocytes, whereas parental or resa3-KO infected erythrocytes remained undamaged. Furthermore, a 6 h exposure of ring stages at 41 degrees C resulted in 33% culture inhibition of resa1-KO parasites while marginally impacting parental and resa3-KO parasite growth. This points to a role for RESA in protecting the infected erythrocyte cytoskeleton during febrile episodes. Infection patterns of resa1-KO and parental parasites in Saimiri sciureus indicated that RESA does not, at least on its own, modulate virulence in the squirrel monkey, as had been previously suggested.
authors.affiliation: Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, Département de Parasitologie, Institut Pasteur, Paris, France.
authors.forename: Monica Diez
authors.initials: MD
authors.lastname: Silva
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cooke
authors.forename: Micheline
authors.initials: M
authors.lastname: Guillotte
authors.forename: Donna W
authors.initials: DW
authors.lastname: Buckingham
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Sauzet
authors.forename: Cecile
authors.initials: C
authors.lastname: Le Scanf
authors.forename: Hugues
authors.initials: H
authors.lastname: Contamin
authors.forename: Peter
authors.initials: P
authors.lastname: David
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Serge
authors.initials: S
authors.lastname: Bonnefoy
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000469:parasitology; D006358:Hot Temperature; D006801:Humans; D016778:Malaria, Falciparum; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*; D012453:Saimiri / Q000469:parasitology
chemical_list: D000953:Antigens, Protozoan; D018955:CD36 Antigens; D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum