Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium.
In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.
Min-Oo
Gundula
G
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montréal, QC, Canada.
Ayi
Kodjo
K
Bongfen
Silayuv E
SE
Tam
Mifong
M
Radovanovic
Irena
I
Gauthier
Susan
S
Santiago
Helton
H
Rothfuchs
Antonio Gigliotti
AG
Roffê
Ester
E
Sher
Alan
A
Mullick
Alaka
A
Fortin
Anny
A
Stevenson
Mary M
MM
Kain
Kevin C
KC
Gros
Philippe
P
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy; D014355:Chagas Disease / Q000188:drug therapy; D002738:Chloroquine / Q000494:pharmacology; D003543:Cysteamine / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005260:Female; D058851:GPI-Linked Proteins; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects
D000962:Antimalarials; D016207:Cytokines; D058851:GPI-Linked Proteins; D006454:Hemoglobins; D003543:Cysteamine; D002738:Chloroquine; D000581:Amidohydrolases; C022314:pantetheinase