, Volume 170, Issue 2, pp 123–130 | Cite as

Paracoccidioides brasiliensis Uses Endogenous and Exogenous Arachidonic Acid for PGEx Production

  • Guilherme Augusto Biondo
  • Luciane Alarcão Dias-Melicio
  • Ana Paula Bordon-Graciani
  • Michele Janegitz Acorci-Valério
  • Angela Maria Victoriano Campos Soares


Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids during fungal infections plays a critical role on fungal biology as well as on host immune response modulation. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, Bt79, Pb192) produce prostaglandin Ex (PGEx). Moreover, we asked if P. brasiliensis could use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) enzyme, as reported for mammalian cells. A possible association between this prostanoid and fungus viability was also assessed. Our results showed that all strains, independently of their virulence, produce high PGEx levels on 4 h culture that were reduced after 8 h. However, in both culture times, higher prostanoid levels were detected after supplementation of medium with exogenous AA. Treatment with indomethacin, a COX inhibitor, induced a reduction on PGEx, as well as in fungus viability. The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability.


Paracoccidioides brasiliensis Prostaglandin Ex Fungal survival Cyclooxygenase 



Conflict of interest statement

There is no conflict of interest.


  1. 1.
    Brock TG, Peters-Golden M. Activation and regulation of cellular eicosanoid biosynthesis. Scientific World Journal. 2007;7:1273–84.PubMedGoogle Scholar
  2. 2.
    Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA. 1999;96:7220–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Betz M, Fox BS. Prostaglandin E2 inhibits production of Th1 lymphokines but not Th2 lymphokines. J Immunol. 1991;146:108–13.PubMedGoogle Scholar
  4. 4.
    Phipps RP, Stein SH, Roper RL. A new view of prostaglandin E regulation of the immune response. Immunol Today. 1991;12:349–52.CrossRefPubMedGoogle Scholar
  5. 5.
    Rocca B, FitzGerald GA. Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol. 2002;2:603–30.CrossRefPubMedGoogle Scholar
  6. 6.
    Harizi H, Gualde N. Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators. Cell Mol Immunol. 2006;3:271–7.PubMedGoogle Scholar
  7. 7.
    San-Blás G. Paracoccidioides brasiliensis: cell wall glucans, pathogenicity and dimorphism. Curr Top Med Mycol. 1985;1:235–57.PubMedGoogle Scholar
  8. 8.
    Franco M, Mendes RP, Moscardi-Bacchi M, Rezkallah-Iwasso MT, Montenegro MR. Paracoccidioidomycosis. Bailliere’s Clin Trop Med Commun Dis. 1989;4:185–220.Google Scholar
  9. 9.
    Franco M, Montenegro MR, Mendes RP, Marques SA, Dillon NL, Mota NG. Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop. 1987;20:129–32.PubMedGoogle Scholar
  10. 10.
    Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an update. Clin Microbiol Rev. 1993;6:89–117.PubMedGoogle Scholar
  11. 11.
    Mendes RP. The gamut of clinical manifestations. In: Franco MF, Lacaz CS, Restrepo A, Del Negro G, editors. Paracoccidioidomycosis. Boca Raton: CRC Press; 1994. p. 233–52.Google Scholar
  12. 12.
    Benard G. An overview of the immunopathology of human Paracoccidioidomycosis. Mycopathologia. 2008;165:209–21.CrossRefPubMedGoogle Scholar
  13. 13.
    Bordon AP, Dias-Melicio LA, Acorci MJ, Biondo GA, Fecchio D, Peraçoli MT, et al. Prostaglandin E(2) production by high and low virulent strains of Paracoccidioides brasiliensis. Mycopathologia. 2007;163:129–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Soares AMVC, Calvi SA, Peraçoli MTS, Fernandez AC, Dias LA, Dos Anjos AR. Modulatory effect of prostaglandins on human monocyte activation for killing of high- and low-virulence strains of Paracoccidioides brasiliensis. Immunology. 2001;102:480–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Noverr NC, Phare SM, Toews GB, Coffey MJ, Huffnagle GB. Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun. 2001;69:2957–63.CrossRefPubMedGoogle Scholar
  16. 16.
    Singer-Vermes LM, Ciavaglia MC, Casino SS, Burger E, Calich VLG. The source of the growth-promoting factor(s) affects the plating efficiency of Paracoccidioides brasiliensis. J Med Vet Mycol. 1992;30:261–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Harizi H, Gualde N. The impact of eicosanoids on the crosstalk between innate and adaptive immunity: the key roles of dendritic cells. Tissue Antigens. 2005;65:507–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Boyce JA. Eicosanoids in asthma, allergic inflammation, and host defense. Curr Mol Med. 2008;8:335–49.CrossRefPubMedGoogle Scholar
  19. 19.
    Bordon AP, Dias-Melicio LA, Acorci MJ, Calvi SA, Serrão Peraçoli MT, Soares AM. Prostaglandin E2 inhibits Paracoccidioides brasiliensis killing by human monocytes. Microbes Infect. 2007;9:744–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Kurokawa CS, Lopes CR, Sugizaki MF, Kuramae EE, Franco MF, Peraçoli MT. Virulence profile of ten Paracoccidioides brasiliensis isolates: association with morphologic and genetic patterns. Rev Inst Med Trop São Paulo. 2005;47:257–62.PubMedGoogle Scholar
  21. 21.
    Noverr MC, Toews GB, Huffnagle GB. Production of prostaglandins and leukotrienes by pathogenic fungi. Infect Immun. 2002;70:400–2.CrossRefPubMedGoogle Scholar
  22. 22.
    Gangopadhyay P, Thadepalli H, Roy I, Ansari A. Identification of species of Candida, Cryptococcus and Torulopsis by gas-liquid chromatography. J Infect Dis. 1979;140:952–8.PubMedGoogle Scholar
  23. 23.
    Marumo K, Aoki Y. Discriminant analysis of cellular fatty acids of Candida species, Torulopsis glabrata and Cryptococcus neoformans determined by gas-liquid chromatography. J Clin Microbiol. 1990;28:1509–13.PubMedGoogle Scholar
  24. 24.
    Botha A, Kock JL, Coetzee DJ, Botes PJ. Physiological properties and fatty acid composition in Mucor circinelloides f. circinelloides. Antonie Van Leeuwenhoek. 1997;71:201–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Lamacka M, Sajbidor J. The content of prostaglandins and their precursors in Mortierella and Cunninghamella species. Lett Appl Microbiol. 1998;26:224–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Pohl CH, Botha A, Kock JL, Coetzee DJ, Botes PJ, Schewe T, et al. Oxylipin formation in fungi: biotransformation of arachidonic acid to 3-hydroxy-5, 8-tetradecadienoic acid by Mucor genevensis. Biochem Biophys Res Commun. 1998;253:703–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Botha A, Paul I, Roux C, Kock JL, Coetzee DJ, Strauss T, et al. An isolation procedure for arachidonic acid producing Mortierella species. Antonie Van Leeuwenhoek. 1999;75:253–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Noverr MC, Erb-Downward JR, Huffnagle GB. Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev. 2003;16:517–33.CrossRefPubMedGoogle Scholar
  29. 29.
    Erb-Downward JR, Huffnagle GB. Cryptococcus neoformans produces authentic prostaglandin E2 without a cyclooxygenase. Eukaryot Cell. 2007;6:346–50.CrossRefPubMedGoogle Scholar
  30. 30.
    Erb-Downward JR, Noverr MC. Characterization of prostaglandin E2 production by Candida albicans. Infect Immun. 2007;75:3498–505.CrossRefPubMedGoogle Scholar
  31. 31.
    Tsitsigiannis DI, Bok JW, Andes D, Nielsen KF, Frisvad JC, Keller NP. Aspergillus cyclooxygenase-like enzymes are associated with prostaglandin production and virulence. Infect Immun. 2005;73:4548–59.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Guilherme Augusto Biondo
    • 1
  • Luciane Alarcão Dias-Melicio
    • 1
  • Ana Paula Bordon-Graciani
    • 1
  • Michele Janegitz Acorci-Valério
    • 1
  • Angela Maria Victoriano Campos Soares
    • 1
  1. 1.Departamento de Microbiologia e Imunologia, Instituto de BiociênciasUNESP – Universidade Estadual PaulistaBotucatuBrazil

Personalised recommendations