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 Legio nella and Chlamydia. These factors share amino acid homology to eukary otic peptidyl-prolyl cis-trans isomerases that are inhibited by FK506, an inhibitor of signal transduction in mammalian cells with potent im munosuppressor activity. We report here the characterization of a prot ein released into the culture medium by the infective stage of the pro tozoan intracellular parasite Trypanosoma cruzi. The protein possesses a peptidyl-prolyl cis-trans isomerase activity that is inhibited by F K506 and its non-immunosuppressing derivative L-685,818. The correspon ding gene presents sequence homology with bacterial macrophage infecti vity potentiators. The addition of the protein, produced heterologousl y in Escherichia coli, to cultures of trypomastigotes and simian epith elial or HeLa cells enhances invasion of the mammalian cells by the pa rasites. Antibodies raised in mice against the T.cruzi isomerase great ly 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.