Characterization of a multicopy family of genes encoding a surface-expressed serine endoprotease in rat Pneumocystis carinii

A unique family of genes encoding serine endoproteases related to the Sacch aromyces cerevisiae serine endoprotease kexin was identified in Pneumocysti s carinii. Unlike previously described serine endoprotease genes that are s ingle copies, multiple copies of the P. carinii serine endoprotease are dis tributed throughout the genome. The proteins predicted by these variant gen es demonstrate sequence variability, but they retain the conserved active s ites associated with endoprotease activity. The serine endoprotease was loc alized to the organism surface by immunohistochemical and immunofluorescenc e studies and to the electron lucent layer of the cyst wall by immunoelectr on microscopy. The findings of multiple copies of the serine endoprotease g ene in the P. carinii genome, and its localization to the cell surface, sug gest that this protease plays an important role in the biology of P. carini i and that antigenic variation of the surface-expressed serine endoprotease may be a strategy for immune evasion. P. carinii serine endoprotease provi des a novel target for chemotherapeutic and immune-based approaches to the treatment of P. carinii pneumonia.