Abstract
Pneumocystis carinii is a yeast-like fungus that dwells exclusively in rats, where it is subjected to the host immune response. Immune pressure is countered by three subtelomeric gene families that generate antigenic diversity in populations of P. carinii. Members of the three gene families are grouped together in tandem arrays that appear to have been generated by recombination and modified by further recombination events after array formation. One of these gene families, MSG, encodes various forms of a major surface glycoprotein. In a given P. carinii organism, all but one of the members of the MSG gene family appear to be transcriptionally silent. The expressed MSG gene is adjacent to a unique locus (the expression site). Different MSG genes can occupy the expression site, suggesting that recombination can take a gene from a pool of silent donors and install it at the expression site, thereby extinguishing transcription of the previous expression site resident, activating transcription of the newly installed MSG gene, and changing the surface of the microbe. Switching at the expression site is probably facilitated by the subtelomeric locations of expressed and silent MSG genes. A second subtelomeric gene family, MSR, is not strictly regulated at the transcriptional level, but may contribute to phenotypic diversity via high-frequency frameshifting caused by coding poly(G) tracts in some MSR genes.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aliouat-Denis, C. M., Chabe, M., Demanche, C., Aliouat, E. M., Viscogliosi, E., Guillot, J., et al. (2008). Pneumocystis species, co-evolution and pathogenic power. Infection, Genetics and Evolution, 8, 708–726.
Ambrose, H. E., Keely, S. P., Aliouat, E. M., Dei-Cas, E., Wakefield, A. E., Miller, R. F., et al. (2004). Expression and complexity of the PRT1 multigene family of Pneumocystis carinii. Microbiology, 150, 293–300.
Barry, J. D., Ginger, M. L., Burton, P., & McCulloch, R. (2003). Why are parasite contingency genes often associated with telomeres? International Journal for Parasitology, 33, 29–45.
Brubaker, R., Redhead, S. A., Stringer, J. R., Keely, S. P., & Cushion, M. T. (2009). Misinformation about Pneumocystis. Clinical and Experimental Dermatology, 34, e426–e427.
Cornillot, E., Keller, B., Cushion, M. T., Metenier, G., & Vivares, C. P. (2002). Fine analysis of the Pneumocystis carinii f. sp. carinii genome by two- dimensional pulsed-field gel electrophoresis. Gene, 293, 87–95.
Cushion, M. T. (1998). Genetic heterogeneity of rat-derived Pneumocystis. FEMS Immunology and Medical Microbiology, 22, 51–58.
Cushion, M. T., & Stringer, J. R. (2005). Has the name really been changed? it has for most researchers. Clinical Infectious Diseases, 41, 1756–1758.
Cushion, M. T., & Stringer, J. R. (2010). Stealth and opportunism: Alternative lifestyles of species in the fungal genus Pneumocystis. Annual Review of Microbiology, 64, 431–452.
Cushion, M. T., Keely, S. P., & Stringer, J. R. (2004). Molecular and phenotypic description of Pneumocystis wakefieldiae sp. nov., a new species in rats. Mycologia, 96, 429–438.
Cushion, M. T., Keely, S. P., & Stringer, J. R. (2005). Validation of the name Pneumocystis wakefieldiae. Mycologia, 97, 268.
Cushion, M. T., Smulian, A. G., Slaven, B. E., Sesterhenn, T., Arnold, J., Staben, C., et al. (2007). Transcriptome of Pneumocystis carinii during fulminate infection: Carbohydrate metabolism and the concept of a compatible parasite. PLoS ONE, 2, e423.
Dei-Cas, E., Chabe, M., Moukhlis, R., Durand-Joly, I., Aliouat, E. M., Stringer, J. R., et al. (2006). Pneumocystis oryctolagi sp. nov., an uncultured fungus causing pneumonia in rabbits at weaning: Review of current knowledge, and description of a new taxon on genotypic, phylogenetic and phenotypic bases. FEMS Microbiology Reviews, 30, 853–871.
Deitsch, K. W., Lukehart, S. A., & Stringer, J. R. (2009). Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nature Reviews Microbiology, 7, 493–503.
DePrimo, S. E., Cao, J., Hersh, M. N., & Stringer, J. R. (1998). Use of human placental alkaline phosphatase transgenes to detect somatic mutation in mice in situ. Methods, 16, 49–61.
Durand-Joly, I., Aliouat, E. M., Recourt, C., Guyot, K., Francois, N., Wauquier, M., et al. (2002). Pneumocystis carinii f. sp. hominis is not infectious for SCID mice. Journal of Clinical Microbiology, 40, 1862–1865.
Edman, J. C., Hatton, T. W., Nam, M., Turner, R., Mei, Q., Angus, C. W., et al. (1996). A single expression site with a conserved leader sequence regulates variation of expression of the Pneumocystis carinii family of major surface glycoprotein genes. DNA and Cell Biology, 15, 989–999.
Eriksson, O. E. (1994). Pneumocystis carinii, a parasite in lungs of mammals, referred to a new family and order (Pneumocystidaceae, Pneumocystidales, Ascomycota). Systema Ascomycetum, 13, 165–180.
Fischer, J. M., Keely, S. P., & Stringer, J. R. (2006). Evolutionary rate of Ribosomal DNA in Pneumocystis species is normal despite the extraordinarily low copy-number of rDNA genes. Journal of Eukaryotic Microbiology, 53(Suppl 1), S156–S158.
Garbe, T. R., & Stringer, J. R. (1994). Molecular characterization of clustered variants of genes encoding major surface antigens of human Pneumocystis carinii. Infection and Immunity, 62, 3092–3101.
Gigliotti, F., Harmsen, A. G., Haidaris, C. G., & Haidaris, P. J. (1993). Pneumocystis carinii is not universally transmissible between mammalian species. Infection and Immunity, 61, 2886–2890.
Haidaris, C. G., Medzihradsky, O. F., Gigliotti, F., & Simpson-Haidaris, P. J. (1998). Molecular characterization of mouse Pneumocystis carinii surface glycoprotein A. DNA Research, 5, 77–85.
Hersh, M. N., Stambrook, P. J., & Stringer, J. R. (2002). Visualization of mosaicism in tissues of normal and mismatch-repair-deficient mice carrying a microsatellite-containing transgene. Mutation Research, 505, 51–62.
Huang, S. N., Angus, C. W., Turner, R. E., Sorial, V., & Kovacs, J. A. (1999). Identification and characterization of novel variant major surface glycoprotein gene families in rat Pneumocystis carinii. Journal of Infectious Diseases, 179, 192–200.
Huang, L., Cattamanchi, A., Davis, J. L., den, B. S., Kovacs, J., Meshnick, S., et al. (2011). HIV-associated Pneumocystis pneumonia. Proceedings of the American Thoracic Society, 8, 294–300.
Keely, S. P., & Stringer, J. R. (2003). Sequence diversity of transcripts from Pneumocystis carinii gene families MSR and PRT1. Journal of Eukaryotic Microbiology, 50(Suppl), 627–628.
Keely, S. P., & Stringer, J. R. (2005). Nomenclature and genetic variation of Pneumocystis. Pneumocystis Pneumonia, 3, 39–59.
Keely, S. P., & Stringer, J. R. (2009). Complexity of the MSG gene family of Pneumocystis carinii. BMC Genomics, 10, 367.
Keely, S. P., Baughman, R. P., Smulian, A. G., Dohn, M. N., & Stringer, J. R. (1996). Source of Pneumocystis carinii in recurrent episodes of pneumonia in AIDS patients. AIDS, 10, 881–888.
Keely, S. P., Cushion, M. T., & Stringer, J. R. (1999). Determination of the maximum frequency of genetic rearrangements associated with Pneumocystis carinii surface antigen variation (In Process Citation). Journal of Eukaryotic Microbiology, 46, 128S.
Keely, S. P., Fischer, J. M., & Stringer, J. R. (2003). Evolution and speciation of Pneumocystis. Journal of Eukaryotic Microbiology, 50(Suppl), 624–626.
Keely, S. P., Fischer, J. M., Cushion, M. T., & Stringer, J. R. (2004). Phylogenetic identification of Pneumocystis murina sp. nov., a new species in laboratory mice. Microbiology, 150, 1153–1165.
Keely, S. P., Renauld, H., Wakefield, A. E., Cushion, M. T., Smulian, A. G., Fosker, N., et al. (2005). Gene arrays at Pneumocystis carinii telomeres. Genetics, 170, 1589–1600.
Keely, S. P., Linke, M. J., Cushion, M. T., & Stringer, J. R. (2007). Pneumocystis murina MSG gene family and the structure of the locus associated with its transcription. Fungal Genetics and Biology, 44, 905–919.
Kutty, G., & Kovacs, J. A. (2003). A single-copy gene encodes Kex1, a serine endoprotease of Pneumocystis jiroveci. Infection and Immunity, 71, 571–574.
Kutty, G., Huang, S. N., & Kovacs, J. A. (2003). Characterization of thioredoxin reductase genes (trr1) from Pneumocystis carinii and Pneumocystis jiroveci. Gene, 310, 175–183.
Liu, Y., Leigh, J. W., Brinkmann, H., Cushion, M. T., Rodriguez-Ezpeleta, N., Philippe, H., et al. (2009). Phylogenomic analyses support the monophyly of Taphrinomycotina, including Schizosaccharomyces fission yeasts. Molecular Biology and Evolution, 26, 27–34.
Lugli, E. B., Allen, A. G., & Wakefield, A. E. (1997). A Pneumocystis carinii multi-gene family with homology to subtilisin-like serine proteases. Microbiology, 143, 2223–2236.
Miller, R. F. (1999). Pneumocystis carinii infection in non-AIDS patients. Current opinion in infectious diseases, 12, 371–377.
Rebholz, S. L., & Cushion, M. T. (2001). Three new karyotype forms of Pneumocystis carinii f. sp. carinii identified by contoured clamped homogeneous electrical field (CHEF) electrophoresis. Journal of Eukaryotic Microbiology, 48(Suppl), 109S–110S.
Redhead, S. A., Cushion, M. T., Frenkel, J. K., & Stringer, J. R. (2006). Pneumocystis and Trypanosoma cruzi: Nomenclature and Typifications. Journal of Eukaryotic Microbiology, 53, 2–11.
Russian, D. A., Andrawis-Sorial, V., Goheen, M. P., Edman, J. C., Vogel, P., Turner, R. E., et al. (1999). Characterization of a multicopy family of genes encoding a surface- expressed serine endoprotease in rat Pneumocystis carinii. Proceedings of the Association of American Physicians, 111, 347–356.
Schaffzin, J. K., & Stringer, J. R. (2000). The major surface glycoprotein expression sites of two special forms of rat Pneumocystis carinii differ in structure. Journal of Infectious Diseases, 181, 1729–1739.
Schaffzin, J. K., & Stringer, J. R. (2004). Expression of the Pneumocystis carinii major surface glycoprotein epitope is correlated with linkage of the cognate gene to the upstream conserved sequence locus. Microbiology, 150, 677–686.
Schaffzin, J. K., Garbe, T. R., & Stringer, J. R. (1999a). Major surface glycoprotein genes from pneumocystis carinii f. sp. ratti. Fungal Genetics and Biology, 28, 214–226.
Schaffzin, J. K., Sunkin, S. M., & Stringer, J. R. (1999b). A new family of Pneumocystis carinii genes related to those encoding the major surface glycoprotein. Current Genetics, 35, 134–143.
Sethi, K. K. (1992). Multiplication of human-derived Pneumocystis carinii in severe combined immunodeficient (SCID) mice. Experientia, 48, 63–66.
Smulian, A. G., Linke, M. J., Cushion, M. T., Baughman, R. P., Frame, P. T., Dohn, M. N., et al. (1994). Analysis of Pneumocystis carinii organism burden, viability and antigens in bronchoalveolar lavage fluid in AIDS patients with pneumocystosis: Correlation with disease severity. AIDS, 8, 1555–1562.
Smulian, A. G., Sesterhenn, T., Tanaka, R., & Cushion, M. T. (2001). The ste3 pheromone receptor gene of Pneumocystis carinii Is surrounded by a cluster of signal transduction genes. Genetics, 157, 991–1002.
Stringer, J. R. (1994). Molecular Genetics of Pneumocystis carinii. In P. D. Walzer (Ed.), Pneumocystis carinii pneumonia (2nd ed., pp.73–90). Inc., New York: Marcel Dekker.
Stringer, J. R. (2002). Pneumocystis. International Journal of Medical Microbiology, 292, 391–404.
Stringer, J. R. (2003). The MSG gene family and antigenic variation in the fungus P. carinii. In A. Craig, A. Scherf (Eds.), Antigenic Variation (pp. 201–223). Amsterdam: Academic Press.
Stringer, J. R. (2007). Antigenic variation in Pneumocystis. Journal of Eukaryotic Microbiology, 54, 8–13.
Stringer, J. R., & Cushion, M. T. (1998). The genome of Pneumocystis carinii. FEMS Immunology and Medical Microbiology, 22, 15–26.
Stringer, J. R., & Keely, S. P. (2001). Genetics of surface antigen expression in Pneumocystis carinii. Infection and Immunity, 69, 627–639.
Stringer, S. L., Hong, S. T., Giuntoli, D., & Stringer, J. R. (1991). Repeated DNA in Pneumocystis carinii. Journal of Clinical Microbiology, 29, 1194–1201.
Stringer, S. L., Garbe, T., Sunkin, S. M., & Stringer, J. R. (1993). Genes encoding antigenic surface glycoproteins in Pneumocystis from humans. Journal of Eukaryotic Microbiology, 40, 821–826.
Stringer, J. R., Beard, C. B., Miller, R. F., & Wakefield, A. E. (2002). A new name (Pneumocystis jirovecii) for Pneumocystis from humans. Emerging Infectious Diseases, 8, 891–896.
Stringer, J. R., Cushion, M. T., & Redhead, S. A. (2006). Reply to weinberg, to hughes, and to limper. Clinical Infectious Diseases, 42, 1212–1214.
Stringer, J. R., Beard, C. B., & Miller, R. F. (2009). Spelling Pneumocystis jirovecii. Emerging Infectious Diseases, 15, 506.
Sunkin, S. M., & Stringer, J. R. (1996). Translocation of surface antigen genes to a unique telomeric expression site in Pneumocystis carinii. Molecular Microbiology, 19, 283–295.
Sunkin, S. M., & Stringer, J. R. (1997). Residence at the expression site is necessary and sufficient for the transcription of surface antigen genes of Pneumocystis carinii. Molecular Microbiology, 25, 147–160.
Sunkin, S. M., Linke, M. J., McCormack, F. X., Walzer, P. D., & Stringer, J. R. (1998). Identification of a putative precursor to the major surface glycoprotein of Pneumocystis carinii. Infection and Immunity, 66, 741–746.
Thomas, C. F, Jr, Leof, E. B., & Limper, A. H. (1999). Analysis of Pneumocystis carinii introns. Infection and Immunity, 67, 6157–6160.
Underwood, A. P., Louis, E. J., Borts, R. H., Stringer, J. R., & Wakefield, A. E. (1996). Pneumocystis carinii telomere repeats are composed of TTAGGG and the subtelomeric sequence contains a gene encoding the major surface glycoprotein. Molecular Microbiology, 19, 273–281.
Wada, M., & Nakamura, Y. (1994). MSG gene cluster encoding major cell surface glycoproteins of rat Pneumocystis carinii. DNA Research, 1, 163–168.
Wada, M., & Nakamura, Y. (1996). Unique telomeric expression site of major-surface-glycoprotein genes of Pneumocystis carinii. DNA Research, 3, 55–64.
Wada, M., Sunkin, S. M., Stringer, J. R., & Nakamura, Y. (1995). Antigenic variation by positional control of major surface glycoprotein gene expression in Pneumocystis carinii. Journal of Infectious Diseases, 171, 1563–1568.
Wright, T. W., Simpson Haidaris, P. J., Gigliotti, F., Harmsen, A. G., & Haidaris, C. G. (1994). Conserved sequence homology of cysteine-rich regions in genes encoding glycoprotein A in Pneumocystis carinii derived from different host species. Infection and Immunity, 62, 1513–1519.
Wright, T. W., Bissoondial, T. Y., Haidaris, C. G., Gigliotti, F., & Haidaris, P. J. (1995a). Isoform diversity and tandem duplication of the glycoprotein A gene in ferret Pneumocystis carinii. DNA Research, 2, 77–88.
Wright, T. W., Gigliotti, F., Haidaris, C. G., & Simpson-Haidaris, P. J. (1995b). Cloning and characterization of a conserved region of human and rhesus macaque Pneumocystis carinii gpA. Gene, 167, 185–189.
Acknowledgments
I would like to thank Saundra Stringer, Ann Wakefield, and Scott Keely for their help and encouragement as the work on Pneumocystis telomeres began, developed, and matured.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Stringer, J.R. (2014). Pneumocystis carinii Subtelomeres. In: Louis, E., Becker, M. (eds) Subtelomeres. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41566-1_5
Download citation
DOI: https://doi.org/10.1007/978-3-642-41566-1_5
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-41565-4
Online ISBN: 978-3-642-41566-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)