Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

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Ma , L , Chen , Z , Huang , D W , Cisse , O H , Rothenburger , J L , Latinne , A , Bishop , L , Blair , R , Brenchley , J M , Chabe , M , Deng , X , Hirsch , V , Keesler , R , Kutty , G , Liu , Y , Margolis , D , Morand , S , Pahar , B , Peng , L , Van Rompay , K K A , Song , X , Song , J , Sukura , A , Thapar , S , Wang , H , Weissenbacher-Lang , C , Xu , J , Lee , C-H , Jardine , C , Lempicki , R A , Cushion , M T , Cuomo , C A & Kovacs , J A 2020 , ' Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species ' , mBio , vol. 11 , no. 2 , e02878-19 . https://doi.org/10.1128/mBio.02878-19

Title: Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species
Author: Ma, Liang; Chen, Zehua; Huang, Da Wei; Cisse, Ousmane H.; Rothenburger, Jamie L.; Latinne, Alice; Bishop, Lisa; Blair, Robert; Brenchley, Jason M.; Chabe, 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.; Kovacs, Joseph A.
Contributor organization: Veterinary Biosciences
Helsinki One Health (HOH)
Antti Sukura / Principal Investigator
Veterinary Pathology and Parasitology
Date: 2020-03-03
Language: eng
Number of pages: 20
Belongs to series: mBio
ISSN: 2150-7511
DOI: https://doi.org/10.1128/mBio.02878-19
URI: http://hdl.handle.net/10138/315702
Abstract: Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.
Subject: 11832 Microbiology and virology
1184 Genetics, developmental biology, physiology
conserved domains
major surface glycoprotein
phylogenetic analysis
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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