Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>

ABSTRACT Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major...

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Autores principales:	Emanuel Schmid-Siegert, Sophie Richard, Amanda Luraschi, Konrad Mühlethaler, Marco Pagni, Philippe M. Hauser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	PCP PacBio sequencing Pneumocystis jirovecii Pneumocystis carinii adhesin gene exchange Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2017977a75fc4480a728eff091404cca
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spelling	oai:doaj.org-article:2017977a75fc4480a728eff091404cca2021-11-15T15:51:55ZMechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>10.1128/mBio.01470-172150-7511https://doaj.org/article/2017977a75fc4480a728eff091404cca2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01470-17https://doaj.org/toc/2150-7511ABSTRACT Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI)-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms of antigenic variation used by this pathogen to escape the human immune system, a strategy commonly used by pathogenic microorganisms. Using a new DNA sequencing technology generating long reads, we could characterize the highly repetitive gene families encoding the proteins that are present on the cellular surface of this pest. These gene families are localized in the regions close to the ends of all chromosomes, the subtelomeres. Such chromosomal localization was found to favor genetic recombinations between members of each gene family and to allow diversification of these proteins continuously over time. This pathogen seems to use a strategy of antigenic variation consisting of the continuous production of new subpopulations composed of cells that are antigenically different. Such a strategy is unique among human pathogens.Emanuel Schmid-SiegertSophie RichardAmanda LuraschiKonrad MühlethalerMarco PagniPhilippe M. HauserAmerican Society for MicrobiologyarticlePCPPacBio sequencingPneumocystis jiroveciiPneumocystis cariniiadhesingene exchangeMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	PCP PacBio sequencing Pneumocystis jirovecii Pneumocystis carinii adhesin gene exchange Microbiology QR1-502
spellingShingle	PCP PacBio sequencing Pneumocystis jirovecii Pneumocystis carinii adhesin gene exchange Microbiology QR1-502 Emanuel Schmid-Siegert Sophie Richard Amanda Luraschi Konrad Mühlethaler Marco Pagni Philippe M. Hauser Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
description	ABSTRACT Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI)-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms of antigenic variation used by this pathogen to escape the human immune system, a strategy commonly used by pathogenic microorganisms. Using a new DNA sequencing technology generating long reads, we could characterize the highly repetitive gene families encoding the proteins that are present on the cellular surface of this pest. These gene families are localized in the regions close to the ends of all chromosomes, the subtelomeres. Such chromosomal localization was found to favor genetic recombinations between members of each gene family and to allow diversification of these proteins continuously over time. This pathogen seems to use a strategy of antigenic variation consisting of the continuous production of new subpopulations composed of cells that are antigenically different. Such a strategy is unique among human pathogens.
format	article
author	Emanuel Schmid-Siegert Sophie Richard Amanda Luraschi Konrad Mühlethaler Marco Pagni Philippe M. Hauser
author_facet	Emanuel Schmid-Siegert Sophie Richard Amanda Luraschi Konrad Mühlethaler Marco Pagni Philippe M. Hauser
author_sort	Emanuel Schmid-Siegert
title	Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
title_short	Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
title_full	Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
title_fullStr	Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
title_full_unstemmed	Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>
title_sort	mechanisms of surface antigenic variation in the human pathogenic fungus <italic toggle="yes">pneumocystis jirovecii</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/2017977a75fc4480a728eff091404cca
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Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus <italic toggle="yes">Pneumocystis jirovecii</italic>

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