Pneumocystis

Abstract

Pneumocystis is a genus of opportunistic fungal pathogens, which cause a type of pneumonia by proliferating extracellularly in the lung alveoli in immunodeficient mammalian hosts. In immune suppressed patients, such as in those with acquired immune deficiency syndrome and individuals undergoing immunosuppressive treatment for cancer or organ transplantation, Pneumocystis pneumonia (PcP) continues to represent an important cause of opportunistic infection, respiratory failure and death. The epidemiology, taxonomy and life cycle features as well as issues related to the transmission of Pneumocystis organisms, initiation of infection, organism interactions with the host and the pathogenesis of PcP are areas of research activities. Good culture methods are not available for sustained in vitro cultivation of any species of Pneumocystis, which is currently viewed as a major challenge to performing experiments on these organisms and precludes genetic manipulations. However, several studies have revealed important insights into the biology of this group of organisms.

Key Concepts:

  • Pneumocystis represents a genus of opportunistic fungi that can colonise healthy mammals (transient infections) and cause severe pneumonia in immune compromised mammals.

  • Genetic studies reveal closest phylogeny of Pneumocystis to the ascomycetous fungi and molecular and biochemical studies further indicate that Pneumocystis represents a unique and diverse group of organisms.

  • Each species of Pneumocystis infects a specific mammalian host (host speciesā€specific) and phylogenetic analyses suggest that the association of Pneumocystis species with their mammalian host species is among the longest known example of coevolution.

  • Pneumocystis undergoes asexual and sexual reproduction; most organisms within the mammalian lung are haploid organisms.

  • Pneumocystis organisms attach to type I lung epithelial cells and proliferate extracellularly in the alveolar spaces.

  • PcP is characterised by intense tissue inflammation that leads to respiratory insufficiency, and can be fatal without treatment.

  • Colonisation by P. jirovecii has been implicated as a comorbidity factor in patients with other pulmonary disorders and those undergoing therapies that affect the host's immune system.

Keywords: AIDS; coevolution; colonisation; fungus; genome; lung alveolus; immunodeficient mammals; opportunistic infection; pneumonia

Figure 1.

Phylogenetic tree based on parsimony analysis of 18S ribosomal deoxyribonucleic acid (rDNA) nucleotide sequence. The percentages of bootstrapped datasets are shown. From Taylor et al. .

Figure 2.

A scheme proposed for the intrapulmonary Pneumocystis life cycle. From Yoshida .

Figure 3.

Electron micrograph of Pneumocystis carinii infection of rat lung. The organisms adhere to thin type I epithelial cells (I) and to one another but not to the larger type II cells (II). Type II cells secrete lung surfactant, which appears as multilamellar bodies within cytoplasmic vesicles (L) and other forms (S) in the alveolar lumen. Vegetative trophic forms (T), and cyst (C) stages form a thick layer of organisms that present a serious barrier to gas exchange between the gaseous phase of the alveolus (top) and the blood capillary (not shown). The spore case (upper right) is crescent shaped, suggesting that the spores (ICBs) have been discharged leaving an empty spore case. Numerous tubular extensions (E) of trophic form cell surfaces are present. Bar, 1 μm. From Kaneshiro et al..

Figure 4.

Comparison of Pneumocystis carinii and rat lung cells. (a) Differential interference (Normarski) optics of P. cariniipneumonia rat lung homogenate. (b) The same field taken under fluorescence optics to show nuclei stained with 4′,6′‐diamino‐2‐phenylindole (DAPI). The nuclei of host cells (arrows) are much larger than those of P. carinii (arrowheads). Bar, 10 μm.

close

References

Aliouat‐Denis CM, Chabé M, Demanche C et al. (2008) Pneumocystis species, co‐evolution and pathogenic power. Infection Genetics and Evolution 8: 708–726.

Banerji S, Wakefield AE, Allen AG et al. (1993) The cloning and characterization of the arom gene of Pneumocystis carinii. Journal of General Microbiology 139: 2901–2914.

Basselin‐Eiweida M, Qiu YH, Lipscomb KJ and Kaneshiro ES (2001) Mechanisms of amino acid and glucose uptake by Pneumocystis carinii. Journal of Eukaryotic Microbiology 48: 155S–156S.

Beck JM and Cushion MT (2009) Pneumocystis workshop: 10th anniversary summary. Eukaryotic Cell 8: 446–460.

Burgess JW, Kottom TJ and Limper AH (2008) Pneumocystis carinii exhibits a conserved meiotic control pathway. Infection and Immunity 76: 417–425.

Chabé M, Aliouat‐Denis CM, Delhaes L et al. (2011) Pneumocystis: from a doubtful unique entity to a group of highly diversified fungal species. FEMS Yeast Research 11: 2–17.

Cheng BH, Liu Y, Xuei X et al. (2010) Microarry studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages. BMC Microbiology 10: 103.

Chin K, Luttrell TD, Roe JD et al. (1999) Putative Pneumocystis dormant forms outside the mammalian host, and long‐term cultures derived from them: initial characterizations. Journal of Eukaryotic Microbiology 46: 95S–99S.

Cushion MT, Collins MS and Linke MJ (2009) Biofilm formation by Pneumocystis spp. Eukaryotic Cell 8: 197–206.

Cushion MT, Keely SP and Stringer JR (2004) Molecular and phenotypic description of Pneumocystis wakefieldiae sp. nov., a new species in rats. Mycologia 96: 429–438.

Cushion MT, Ruffolo JJ, Linke MJ and Walzer PD (1985) Pneumocystis carinii: growth variables and estimates in the A549 and WI‐38 VA13 human cell lines. Experimental Parasitology 60: 43–54.

Cushion MT, Smulian AG, Slaven BE et al. (2007) Transcriptome of Pneumocystis carinii during fulminate infection: carbohydrate metabolism and the concept of a compatible parasite. PloS One 2: e423.

Daly KR, Huang L, Morris A et al. (2006) Antibody response to Pneumocystis jirovecii major surface glycoprotein. Emerging Infectious Diseases 12(8): 1231–1237.

Dei‐Cas E, Chabé M, Moukhlis 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 Microbiological Reviews 30: 853–871.

Delanoë P and Delanoë M (1912) Sur les rapports des kystes de Carinii du poumon des rats avec le Trypanosoma lewisii. Comptes rendus de l'Académie des sciences (Paris) 155: 658–660.

DeStefano JA, Myers JD, Du Pont D et al. (1998) Cell wall antigens of Pneumocystis carinii trophozoites and cysts; purification and carbohydrate analysis of these glycoproteins. Journal of Eukaryotic Microbiology 45: 334–343.

Eriksson OE (1994) Pneumocystis carinii, a parasite in lungs of mammals referred to a new family and order (Pneumocystidaceae, Pneumocystidales, Ascomycota). Systema Ascomycetum 13: 165–180.

Gigliotti F, Harmsen AG, Haidaris CG and Haidaris PJ (1993) Pneumocystis carinii is not universally transmissible between mammalian species. Infection and Immunity 61: 2886–2890.

Giner J‐L, Zhao H, Amit Z and Kaneshiro ES (2004) Sterol composition of Pneumocystis jirovecii with blocked 14α‐demethylase activity. Journal of Eukaryotic Microbiology 51: 634–643.

Hauser PM, Burdet FX, Cissé OH et al. (2010) Comparative genomics suggests that the fungal pathogen Pneumocsytis is an obligate parasite scavenging amino acids from its host's lungs. PloS One 5: e15152.

Hibbett DS, Binder M, Bischoff M et al. (2007) A higher level phylogenetic classification of the fungi. Mycological Research 111: 509–547.

Hoffman AGD, Lawrence MG, Ognibene FP et al. (1992) Reduction of pulmonary surfactant in patients with human immunodeficiency virus infection and Pneumocystis carinii pneumonia. Chest 102: 1730–1738.

Kaneshiro ES (1998) The lipids of Pneumocystis carinii. Clinical Microbiological Reviews 11: 27–41.

Kaneshiro ES (2010) Biochemical research elucidating metabolic pathways in Pneumocystis. Parasite 17: 285–291.

Kaneshiro ES, Rosenfeld JA, Basselin M et al. (2002) The Pneumocystis carinii drug target S‐adenosyl‐l‐methionine:sterol methyl transferase has a unique substrate preference. Molecular Microbiology 44: 989–999.

Kaneshiro ES, Wyder MA, Zhou LH et al. (1993) Characterization of Pneumocystis carinii preparations developed for lipid analysis. Journal of Eukaryotic Microbiology 40: 805–815.

Keely SP and Stringer JR (2009) Complexity of the MSG gene family of Pneumocystis carinii. BMC Genomics 10: 367. doi: 10.1186/1471‐2164‐10‐367.

Keely SP, Fischer JM, Cushion MT and Stringer JR (2004) Phylogenetic identification of Pneumocystis murina sp nov., a new species in laboratory mice. Microbiology 150: 1153–1165.

Kutty G, Maldarelli F, Achaz G and Kovacs JA (2008) Variation in the major surface glycoprotein genes in Pneumocystis jirovecii. Journal of Infectious Diseases 198(5): 741–749.

Limper AH, Thomas CF Jr, Anders RA and Leof EB (1997) Interactions of parasite and host epithelial cell cycle regulation during Pneumocystis carinii pneumonia. Journal of Laboratory and Clinical Medicine 130: 132–138.

Lundgren B, Lipschik GY and Kovacs JA (1991) Purification and characterization of a major human Pneumocystis carinii surface antigen. Journal of Clinical Investigation 87: 163–170.

Matos O and Esteves F (2010) Epidemiology and clinical relevance of Pneumocystis jirovecii Frenkel, 1976 dihydropteroate synthase gene mutations. Parasite 17: 219–232.

Moncada CA, Clarkson A, Perez‐Leal O and Merali S (2008) Mechanism and tissue specificity of nicotine‐mediated lung S‐adenosylmethionine reduction. Journal of Biological Chemistry 283: 7690–7696.

Morris A, Crothers K, Beck JM and Huang L; on behalf of the American Thoracic Society Committee on HIV Pulmonary Disease (2011) An official ATS workshop report: emerging issues and current controversies in HIV‐associated pulmonary diseases. Proceedings of the American Thoracic Society 8(1): 17–26.

O'Riordan DM, Standing JE, Kwon KY et al. (1995) Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophage. Journal of Clinical Investigation 95: 2699–2710.

Pifer LL, Hughes WT, Stagno S and Woods D (1978) Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 62: 35–41.

Redhead SA, Cushion MT, Frenkel JK and Stringer JR (2006) Pneumocystis and Trypanosoma cruzi: nomenclature and typifications. Journal of Eukaryotic Microbiology 53: 2–11.

Sesterhenn TM, Slaven BE, Keely SP et al. (2010) Sequence and structure of the linear mitochondrial genome of Pneumocystis carinii. Molecular Genetics and Genomics 283: 63–72.

Shivii M, Berger S, Moncada CA et al. (2005) Effect of nicotine on lung S‐adenosylmethionine and development of Pneumocystis pneumonia. Journal of Biological Chemistry 280: 15219–15228.

Smulian AG, Sesterhenn T, Tanaka R and Cushion MT (2001) The ste3 pheromone receptor gene of Pneumocystis carinii is surrounded by a cluster of signal transduction genes. Genetics 157: 991–1002.

Stringer JR (2007) Antigenic variation in Pneumocystis. Journal of Eukaryotic Microbiology 54: 8–13.

Taylor JW, Swann EC and Berbee ML (1994) Molecular evolution of ascomycete fungi: phylogeny and conflict. In: Hawksworth DL (ed.) Ascomycete Systematics. Problems and Perspectives in the Nineties, pp. 201–212. New York: Plenum Press.

Thomas CF Jr and Limper AH (1998) Pneumocystis pneumonia: clinical presentation and diagnosis in patients with and without acquired immune deficiency syndrome. Seminars in Respiratory Infections 13: 289–295.

Thomas CF Jr and Limper AH (2007) Current insights into the biology and pathogenesis of Pneumocystis pneumonia. Nature Reviews. Microbiology 5: 298–308.

Vassallo R, Standing JE and Limper AH (2000) Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses. Journal of Immunology 164: 3755–3763.

Wakefield AE (1996) DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. Journal of Clinical Microbiology 34: 1754–1759.

Wright TW, Gigliotti F, Finkelstein JN et al. (1999) Immune‐mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis carinii pneumonia. Journal of Clinical Investigation 104: 1307–1317.

Yoshida Y (1989) Ultrastructural studies of Pneumocystis carinii. Journal of Protozoology 36: 53–60.

Further Reading

Calderón EJ, Gutiérrez‐Rivero S, Durand‐Joly I and Dei‐Cas E (2010) Pneumocystis infection in humans: diagnosis and treatment. Expert Reviews of Anti‐Infection Therapy 8: 683–701.

Cushion MT (2010) Chapter 37. Pneumocystis pneumonia. In: MerzWG and Hay RJ (eds) Topley and Wilson's Microbiology and Microbial Infections. Medical Microbiology, Part VI. Systemic Mycosis Caused by Opportunistic Fungi, 10th edn, pp. 763–806, Washington, DC: ASM Press.

Dei‐CasE and Cailliez J‐C (eds) (1998) Pneumocystis carinii. FEMS Immunology and Medical Microbiology, vol. 22, pp. 1–189.

Girard P‐M and Bozzette SA (1995) Strategies for Prophylaxis of Pneumocystis carinii Pneumonia. Ballière's Clinical Infectious Diseases, 1st edn, pp. 551–571, London: Ballière Tindall.

Huang L (2011) Clinical and translational research in Pneumocystis and Pneumocystis pneumonia. Parasite 18(1): 3–11.

Kaplan JE, Hanson DL, Jones JL et al. (1998) Opportunistic infections (OIs) as emerging infectious diseases: challenges posed by OIs in the 1990s and beyond. In: Scheld WM, Craig W and Hughes JM (eds) Emerging Infections 2, pp. 257–272. Washington, DC: ASM Press.

Kovacs JA and Masur H (2009) Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. Journal of the American Medical Association 301(24): 2578–2585.

Stringer JR (1996) Pneumocystis carinii: what is it exactly? Clinical Microbiological Reviews 9: 489–498.

Thomas CF Jr and Limper AH (2004) Pneumocystis pneumonia. New England Journal of Medicine 350: 2487–2498.

Walzer PD and Cushion MT (eds) (2004) Pneumocystis Pneumonia, 3rd edn. New York: Marcel Dekkar.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Kaneshiro, Edna S, and Limper, Andrew H(Aug 2011) Pneumocystis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002101.pub2]