DEVELOPMENTALLY-REGULATED EXPRESSION OF A NOVEL 59-KDA PRODUCT OF THEMAJOR SURFACE PROTEASE (MSP OR GP63) GENE FAMILY OF LEISHMANIA-CHAGASI

All species of Leishmania express a major surface protease (Msp or gp6 3) that facilitates the interactions of the parasite with its environm ent at several steps in its life cycle. The msp gene family in Leishma nia chagasi contains three classes of genes whose mRNAs are differenti ally expressed during parasite growth, Logarithmic phase (low infectiv ity) promastigotes express only 63-kDa versions of Msp, whereas statio nary phase (high infectivity) promastigotes express both 63- and 59-kD a Msps. The different migrations of the 59- and 63-kDa proteins on acr ylamide gels are not due to differences in N-linked glycosylation or t he membrane anchor. Plasmid transfections of Leishmania demonstrate th at mspS2 of the stationary gene class encodes a 59 kDa protein. Expres sion of the 59-kDa protein in stationary phase promastigotes ceases af ter about 12 weeks of in vitro cultivation when the parasites become a ttenuated. Attenuated parasites can be stimulated to re express the 59 -kDa Msp by passage through mice followed by several in vitro passages of recovered promastigotes. Amastigotes express yet another subset of Msp proteins. Thus, the 59-kDa product of mspS2 is expressed only in stationary phase promastigotes and only after recent exposure to envir onmental changes encountered in the mammalian host cell.