A role for the Plasmodium falciparum RESA protein in resistance against heat shock demonstrated using gene disruption.
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.
Silva
Monica Diez
MD
Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, Département de Parasitologie, Institut Pasteur, Paris, France.
Cooke
Brian M
BM
Guillotte
Micheline
M
Buckingham
Donna W
DW
Sauzet
Jean-Pierre
JP
Le Scanf
Cecile
C
Contamin
Hugues
H
David
Peter
P
Mercereau-Puijalon
Odile
O
Bonnefoy
Serge
S
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
D000953:Antigens, Protozoan; D018955:CD36 Antigens; D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum