Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii
| Autor: | Emanuel Schmid-Siegert, Sophie Richard, Amanda Luraschi, Konrad Muhlethaler, Marco Pagni, Philippe M. Hauser, Louis M. Weiss |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pseudogene Biology Pneumocystis carinii Microbiology 03 medical and health sciences adhesin Virology Antigenic variation gene exchange Gene family Pneumocystis jirovecii Ectopic recombination Pathogen Gene 030304 developmental biology 2. Zero hunger Genetics chemistry.chemical_classification 0303 health sciences PacBio sequencing 030306 microbiology Subtelomere biology.organism_classification QR1-502 PCP 030104 developmental biology chemistry Antigenic Variation Antigens Fungal/genetics Antigens Fungal/immunology Bronchoalveolar Lavage Fluid/microbiology DNA Fungal/genetics Fungal Proteins/genetics Fungal Proteins/immunology Fungal Proteins/isolation & purification Glycosylphosphatidylinositols/chemistry Glycosylphosphatidylinositols/metabolism Humans Membrane Glycoproteins/genetics Membrane Glycoproteins/immunology Membrane Glycoproteins/metabolism Mosaicism Nucleotide Motifs Pneumocystis carinii/chemistry Pneumocystis carinii/genetics Pneumocystis carinii/immunology Pneumocystis carinii/pathogenicity Pneumonia Pneumocystis/immunology Pneumonia Pneumocystis/microbiology Pseudogenes/genetics Sequence Analysis DNA major surface glycoprotein mosaicism subtelomere telomere exchange Glycoprotein |
| Zdroj: | mBio, Vol 8, Iss 6 (2017) mBio, vol. 8, no. 6, pp. e01470-17 Schmid-Siegert, Emanuel; Richard, Sophie; Luraschi, Amanda; Mühlethaler, Konrad; Pagni, Marco; Hauser, Philippe M (2017). Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii. mBio, 8(6) American Society for Microbiology 10.1128/mBio.01470-17 mBio, Vol 8, Iss 6, p e01470-17 (2017) |
| ISSN: | 2150-7511 |
| DOI: | 10.1128/mBio.01470-17 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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