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Effect of inhibitors of arachidonic acid metabolism on prostaglandin E2 production by Candida albicans and Candida dubliniensis biofilms

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Abstract

Arachidonic acid (AA) is released from infected host cells during Candida albicans infection and may serve as carbon source for yeast growth and as precursor for the production of biologically active eicosanoids, such as prostaglandin E2 (PGE2) by C. albicans. However, the mechanism involved in this production is still unclear. Therefore, it was of interest to investigate the effect of different arachidonic acid metabolism inhibitors on PGE2 production by biofilms of C. albicans and the closely related C. dubliniensis. This was done by growing Candida biofilms in the presence of AA as well as cytochrome P450 (CYP), multicopper oxidase, cyclooxygenase or lipoxygenase inhibitors. The concentration of PGE2 was determined by a monoclonal PGE2 enzyme-linked immunosorbent assay and verified with LCMS/MS. The results obtained indicate the ability of C. albicans and C. dubliniensis biofilms to produce PGE2 from exogenous AA. The use of different inhibitors suggested that CYPs and multicopper oxidases are involved in PGE2 production by these Candida biofilms.

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References

  1. Sullivan DJ, Westerneng TJ, Haynes KA, Bennett DE, Coleman DC (1995) Candida dubliniensis sp. nov.: phenotypic and molecular characterisation of a novel species associated with oral candidosis in HIV infected individuals. Microbiology 141:1507–1521

    Article  CAS  PubMed  Google Scholar 

  2. Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL (2001) Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother 45:2475–2479

    Article  CAS  PubMed  Google Scholar 

  3. Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL (2001) Biofilm formation by C. dubliniensis. J Clin Microbiol 39:3234–3240

    Article  CAS  PubMed  Google Scholar 

  4. Brash AR (2001) Arachidonic acid as a bioactive molecule. J Clin Invest 107:1339–1345

    Article  CAS  PubMed  Google Scholar 

  5. Deva R, Ciccoli R, Kock JLF, Nigam S (2001) Involvement of aspirin-sensitive oxylipins in vulvovaginal candidiasis. FEMS Microbiol Lett 198:37–43

    Article  CAS  PubMed  Google Scholar 

  6. Noverr MC, Erb-Downward JC, Huffnagle GB (2003) Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev 16:517–533

    Article  CAS  PubMed  Google Scholar 

  7. Deva R, Ciccoli R, Schewe T, Kock JLF, Nigam S (2000) Arachidonic acid stimulates cell growth and forms a novel oxygenated metabolite in Candida albicans. Biochim Biophys Acta 1486:299–311

    CAS  PubMed  Google Scholar 

  8. Noverr MC, Phare SM, Toews GB, Coffey MJ, Huffnagle GB (2001) Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun 69:2957–2963

    Article  CAS  PubMed  Google Scholar 

  9. Noverr MC, Huffnagle GB (2004) Regulation of Candida albicans morphogenesis by fatty acid metabolites. Infect Immun 72:6206–6210

    Article  CAS  PubMed  Google Scholar 

  10. Erb-Downward JR, Noverr MC (2007) Characterisation of prostaglandin E2 production by Candida albicans. Infect Immun 75:3498–3505

    Article  CAS  PubMed  Google Scholar 

  11. Erb-Downward JR, Noggle RM, Williamson PR, Huffnagle GB (2008) The role of laccase in prostaglandin production by Cryptococcus neoformans. Mol Microbiol 68:1428–1437

    Article  CAS  PubMed  Google Scholar 

  12. Wang MH, Brand-Schieber E, Zand BA, Nguyen X, Falck JR, Balu N, Schwartzman ML (1997) Cytochrome P450-Derived arachidonic acid metabolism in the rat kidney: Characterization of selective inhibitors. J Pharmacol Exp Ther 284:966–973

    Google Scholar 

  13. Su P, Maya K, Kroetz DL (1998) Inhibition of renal arachidonic acid ω-hydroxylase activity with ABT reduces blood pressure in the SHR. Am J Physiol Regul Integr Comp Physiol 275:426–438

    Google Scholar 

  14. Imig JD, Falck JR, Inscho EW (1999) Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness. Br J Pharmacol 127:1399–1405

    Article  CAS  PubMed  Google Scholar 

  15. Haas-Stapleton EJ, Lu Y, Hong S, Arita M, Favoreto S, Nigam S, Serhan CN, Agabian N (2007) Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator Resolvin E1. PloS ONE 2(12):e1316. doi:10.1371/journal.pone.0001316

  16. Elmer WK, Stephen DA, William MJ (1992) Laboratory approach to the diagnosis of fungal infections, 14th edn. JP Lipincott company, Philadelphia, pp 387–840

    Google Scholar 

  17. Bachmann SP, Vande Walle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, Lopez-Ribot JL (2002) In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 46:3591–3596

    Article  CAS  PubMed  Google Scholar 

  18. Alem MAS, Douglas LJ (2005) Prostaglandin production during growth of Candida albicans biofilms. J Med Microbiol 54:1001–1005

    Article  CAS  PubMed  Google Scholar 

  19. Johannes C, Majcherczyk A (2000) Laccase activity tests and laccase inhibitors. J Biotech 78:193–199

    Article  CAS  Google Scholar 

  20. Nieves D, Moreno JJ (2006) Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth. J Lipid Res 47:2681–2689

    Article  CAS  PubMed  Google Scholar 

  21. Capdevila J, Gil L, Orellana M, Marnett LJ, Mason JI, Yadagiri P, Falck JR (1988) Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism. Arch Biochem Biophys 261:257–263

    Article  CAS  PubMed  Google Scholar 

  22. Agarwal R, Wang ZY, Bik DP, Mukhtar H (1991) Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450 mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab Dispos 19:620–624

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the National Research Foundation, South Africa, for funding under the Thuthuka programme (Grant number TTK2007041000014) and the Blue Skies programme (Grant number BS2008092300002).

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Correspondence to Carolina H. Pohl.

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Ells, R., Kock, J.L.F., Albertyn, J. et al. Effect of inhibitors of arachidonic acid metabolism on prostaglandin E2 production by Candida albicans and Candida dubliniensis biofilms. Med Microbiol Immunol 200, 23–28 (2011). https://doi.org/10.1007/s00430-010-0169-7

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  • DOI: https://doi.org/10.1007/s00430-010-0169-7

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