Diversity and complexity of the large surface protein superfamily in the genomes of various Pneumocystis species. Pneumocystis sp

Cell surface proteins play an important role in pathogen-host interactions. Pneumocystis, a major opportunistic pathogen in immunodeficient patients, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface protein (Msg) gene superfamily. The msg sequences account for 3-6% of an otherwise highly compacted genome, suggesting an essential role in the organism’s survival in the host environment. Recent genome sequencing has permitted identification of the nearly complete set of msg genes in P. murina, P. carinii and P. jirovecii, which infect mice, rats and human, respectively. In this report we provide an update on identification and classification of msg genes including those from other Pneumocystis species, describe the Msg domain structure and characteristics of each individual Msg family and subfamily, and characterize the msg expression site in Pneumocystis from 10 different mammalian host species. Based on this analysis, msg genes show conservation among msg families and subfamilies across different Pneumocystis species, as well as species-specific expansions or contractions. The versatility of these proteins may mirror their association with a variety of functions, including antigenic variation to allow immune evasion, and optimal adaptation to diverse environmental conditions to promote persistence and colonization in hosts. Our analysis provides a rich source of information that lays the foundation for the continued experimental exploration of the function of the Msg superfamily in Pneumocystis biology. Overall design: Full-length msg genes and/or their expression sites in Pneumocystis from various laboratory and wild mammalian host species were characterized by Sanger sequencing of cloned amplicons, next-generation sequencing and restriction fragment length polymorphism analysis.