title: Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts.
abstract: Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses.
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Da Wei
authors.initials: da W
authors.lastname: Huang
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Geetha
authors.initials: G
authors.lastname: Kutty
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Honghui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Amr
authors.initials: A
authors.lastname: Abouelleil
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bishop
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Davey
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deng
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Xilong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fantoni
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fitzgerald
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Emile
authors.initials: E
authors.lastname: Gogineni
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goldberg
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Handley
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Huber
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Jones
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Levin
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Pendexter
authors.initials: P
authors.lastname: Macdonald
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Melnikov
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Castle
authors.initials: C
authors.lastname: Raley
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Sassi
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Sherman
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Song
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Sykes
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Bao
authors.initials: B
authors.lastname: Tran
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Walsh
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Young
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Qiandong
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Stephens
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.affiliation: Leidos BioMedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Christina A
authors.identifier: http://orcid.org/0000-0002-5778-960X
authors.initials: CA
authors.lastname: Cuomo
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D002473:Cell Wall / Q000378:metabolism; D016681:Genome, Fungal; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000382:microbiology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D005810:Multigene Family; D045363:Pneumocystis carinii / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D026801:Synteny