CONSERVED SEQUENCE HOMOLOGY OF CYSTEINE-RICH REGIONS IN GENES ENCODING GLYCOPROTEIN-A IN PNEUMOCYSTIS-CARINII DERIVED FROM DIFFERENT HOST SPECIES

Pneumocystis carinii surface glycoprotein A (gpA) exhibits host specie s-specific phenotypic and genotypic variation. Despite this heterogene ity, the gpAs of P. carinii isolated from different host species appea r to be homologous molecules sharing certain biochemical and antigenic characteristics. Using two degenerate oligodeoxyribonucleotide primer s corresponding to conserved cysteine regions from ferret and rat P. c arinii gpAs, a PCR product of approximately 300 bp was amplified from ferret, rat, and SCID mouse P. carinii-infected lung genomic DNA. Nort hern (RNA) hybridization revealed a transcript of 3,450 nucleotides in P. carinii-infected SCID mouse lung mRNA, which is similar in size to the transcripts for ferret and rat P. carinii gpAs. Nucleotide sequen ce analysis of SCID mouse P. carinii gpA subclones derived from the PC R products identified two isoforms, which were 89% identical to each o ther in the amplified region and 73 and 54% identical to the rat- and ferret-derived P. carinii gpA genes, respectively. Comparison of the d educed amino acid sequences of mouse, ferret, and rat P. carinii gpAs revealed striking similarity in residues adjacent to and including the conserved cysteines. Furthermore, the spacing of two proline residues is invariant, and a potential N-linked glycosylation site is found at a similar position in all of the gpAs. Despite the heterogeneity obse rved in P. carinii gpAs, the conservation of cysteine residues and adj acent sequences implies similar secondary structure and, most likely, similar function for the gpAs of P. carinii isolated from different ho st species.