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

doi:10.1128/mBio.02878-19

mBio (Apr 2020)

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

DOI: https://doi.org/10.1128/mBio.02878-19
Journal volume & issue: Vol. 11, no. 2

Abstract

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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.

Published in mBio

ISSN: 2161-2129 (Print); 2150-7511 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/mbio

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