Secretion by Trypanosoma cruzi of a peptidyl-prolyl cis-trans isomerase involved in cell infection.
Macrophage infectivity potentiators are membrane proteins described as virulence factors in bacterial intracellular parasites, such as Legionella and Chlamydia. These factors share amino acid homology to eukaryotic peptidyl-prolyl cis-trans isomerases that are inhibited by FK506, an inhibitor of signal transduction in mammalian cells with potent immunosuppressor activity. We report here the characterization of a protein released into the culture medium by the infective stage of the protozoan intracellular parasite Trypanosoma cruzi. The protein possesses a peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and its non-immunosuppressing derivative L-685,818. The corresponding gene presents sequence homology with bacterial macrophage infectivity potentiators. The addition of the protein, produced heterologously in Escherichia coli, to cultures of trypomastigotes and simian epithelial or HeLa cells enhances invasion of the mammalian cells by the parasites. Antibodies raised in mice against the T.cruzi isomerase greatly reduce infectivity. A similar reduction of infectivity is obtained by addition to the cultures of FK506 and L-685,818. We concluded that the T.cruzi isomerase is involved in cell invasion.
Moro
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Instituto de Parasitología y Biomedicina, CSIC, Granada, Spain.
Ruiz-Cabello
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Fernández-Cano
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Stock
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González
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D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D017125:Genes, Protozoan; D006367:HeLa Cells; D006801:Humans; D020104:Immunophilins; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity
D000913:Antibodies, Protozoan; D001426:Bacterial Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D016054:DNA, Protozoan; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000591:Amino Acid Isomerases; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase; C068254:FkpA protein, E coli; D016559:Tacrolimus