Microtubule inhibitors block Cryptosporidium parvum infection of a human enterocyte cell line.
No effective therapy exists for Cryptosporidium parvum, a coccidial protozoan parasite that causes severe diarrhea in patients with AIDS. The role of microtubules in parasite invasion of host cells was investigated by incubating 10(7) oocysts with a HT 29.74 cell line for 24 h in the presence of microtubule-disrupting drugs. The number of parasites per 1,000 cells was reduced by 77% (P < 0.001, n = 4) from 182 +/- 3 in untreated cells to 42 +/- 4 in cells treated with 10(-4) M colchicine. Inhibition of C. parvum infection was concentration dependent. Similar results were seen with a second microtubular depolymerization agent, vinblastine. These data suggest that microtubules are important in host cell invasion by C. parvum and may represent targets for development of new therapeutic drugs for treatment of cryptosporidiosis.
Wiest
P M
PM
International Health Institute, Miriam Hospital, Brown University, Providence, Rhode Island 02906.
Johnson
J H
JH
Flanigan
T P
TP
D000818:Animals; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology*; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000472:pathogenicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007422:Intestines / Q000469:parasitology*; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine; D003078:Colchicine