Diversity and complexity of the large surface protein family in the compacted genomes of variousPneumocystisspecies

Author:

Ma LiangORCID,Chen Zehua,Huang Da Wei,Cissé Ousmane H.ORCID,Rothenburger Jamie L.,Latinne Alice,Bishop Lisa,Blair Robert,Brenchley Jason M.,Chabé Magali,Deng Xilong,Hirsch Vanessa,Keesler Rebekah,Kutty Geetha,Liu Yueqin,Margolis Daniel,Morand Serge,Pahar Bapi,Peng Li,Van Rompay Koen K.A.,Song Xiaohong,Song Jun,Sukura Antti,Thapar Sabrina,Wang Honghui,Weissenbacher-Lang Christiane,Xu Jie,Lee Chao-Hung,Jardine Claire,Lempicki Richard A.,Cushion Melanie T.,Cuomo Christina A.ORCID,Kovacs Joseph A.ORCID

Abstract

AbstractPneumocystis,a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in allPneumocystisspecies characterized to date, highlighting its important role inPneumocystisbiology. In this report, through a comprehensive and in-depth characterization of 459msggenes from 7Pneumocystisspecies, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins, and provide detailed description of the classification, unique characteristics and phylogenetic relatedness of five Msg families. We further describe the relative expression levels of individualmsgfamilies in two rodentPneumocystisspecies, the substantial variability of themsgrepertoires inP. cariniifrom laboratory and wild rats, and the distinct features of the expression site for the classicmsggenes inPneumocystisfrom 8 mammalian host species. Our analysis suggests a wide variety of functions for this superfamily, not only conferring antigenic variation to allow immune evasion but also mediating life-stage development, optimizing cell mobility and adhesion, and adapting to specific host niches or environmental conditions. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily inPneumocystisbiology.

Publisher

Cold Spring Harbor Laboratory

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