Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple <italic toggle="yes">Pneumocystis</italic> Species
Liang Ma,
Zehua Chen,
Da Wei Huang,
Ousmane H. Cissé,
Jamie L. Rothenburger,
Alice Latinne,
Lisa Bishop,
Robert Blair,
Jason M. Brenchley,
Magali Chabé,
Xilong Deng,
Vanessa Hirsch,
Rebekah Keesler,
Geetha Kutty,
Yueqin Liu,
Daniel Margolis,
Serge Morand,
Bapi Pahar,
Li Peng,
Koen K. A. Van Rompay,
Xiaohong Song,
Jun Song,
Antti Sukura,
Sabrina Thapar,
Honghui Wang,
Christiane Weissenbacher-Lang,
Jie Xu,
Chao-Hung Lee,
Claire Jardine,
Richard A. Lempicki,
Melanie T. Cushion,
Christina A. Cuomo,
Joseph A. Kovacs
Affiliations
Liang Ma
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Zehua Chen
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Da Wei Huang
Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
Ousmane H. Cissé
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Jamie L. Rothenburger
Department of Pathobiology, Canadian Wildlife Health Cooperative, Ontario Veterinary College, University of Guelph, Ontario, Canada
Alice Latinne
EcoHealth Alliance, New York, New York, USA
Lisa Bishop
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Robert Blair
Tulane National Primate Research Center, Tulane University, New Orleans, Louisiana, USA
Jason M. Brenchley
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Magali Chabé
Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019–UMR 8204–CIIL–Centre d’Infection et d’Immunité de Lille, Lille, France
Xilong Deng
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Vanessa Hirsch
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Rebekah Keesler
California National Primate Research Center, University of California, Davis, Davis, California, USA
Geetha Kutty
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Yueqin Liu
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Daniel Margolis
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Serge Morand
Institut des Sciences de l’Evolution, Université de Montpellier 2, Montpellier, France
Bapi Pahar
Tulane National Primate Research Center, Tulane University, New Orleans, Louisiana, USA
Li Peng
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Koen K. A. Van Rompay
California National Primate Research Center, University of California, Davis, Davis, California, USA
Xiaohong Song
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Jun Song
Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, Michigan, USA
Antti Sukura
Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
Sabrina Thapar
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Honghui Wang
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Christiane Weissenbacher-Lang
Department of Pathobiology, Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
Jie Xu
Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, Michigan, USA
Chao-Hung Lee
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Claire Jardine
Department of Pathobiology, Canadian Wildlife Health Cooperative, Ontario Veterinary College, University of Guelph, Ontario, Canada
Richard A. Lempicki
Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
Melanie T. Cushion
Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
Christina A. Cuomo
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Joseph A. Kovacs
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
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 Pneumocystis 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. carinii 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 immunodepleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs ∼$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.
