Advertisement

Sphingolipid Signaling in Fungal Pathogens

  • Ryan Rhome
  • Maurizio Del Poeta
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 688)

Abstract

Sphingolipid involvement in infectious disease is a new and exciting branch of research. Various microbial pathogens have been shown to synthesize their own sphingolipids and some have evolved methods to “hijack” host sphingolipids for their own use. For instance, Sphingomonas species are bacterial pathogens that lack the lipopolysaccharide component typical but instead contain glycosphingolipids (Kawahara 1991, 2006). In terms of sphingolipid signaling and function, perhaps the best-studied group of microbes is the pathogenic fungi.

Pathogenic fungi still represent significant problems in human disease, despite treatments that have been used for decades. Because fungi are eukaryotic, drug targets in fungi can have many similarities to mammalian processes. This often leads to significant side effects of antifungal drugs that can be dose limiting in many patient populations. The search for fungal?specific drugs and the need for better understanding of cellular processes of pathogenic fungi has led to a large body of research on fungal signaling. One particularly interesting and rapidly growing field in this research is the involvement of fungal sphingolipid pathways in signaling and virulence. In this chapter, the research relating to sphingolipid signaling pathogenic fungi will be reviewed and summarized, in addition to highlighting pathways that show promise for future research.

Keywords

Cryptococcus Neoformans ATF2 Transcription Factor Ulatory Molecule Sphingolipid Signaling Inositol Phosphos 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hanada K. Sphingolipids in infectious diseases. Jpn J Infect Dis 2005; 58(3):131–148.PubMedGoogle Scholar
  2. 2.
    Heung LJ, Luberto C, Del Poeta M. Role of sphingolipids in microbial pathogenesis. Infect Immun 2006; 74(1):28–39.CrossRefPubMedGoogle Scholar
  3. 3.
    Kawahara K, Sato N, Tsuge K, Seto Y. Confirmation of the anomeric structure of galacturonic acid in the galacturonosyl-ceramide of Sphingomonas yanoikuyae. Microbiol Immunol 2006; 50(1):67–71.PubMedGoogle Scholar
  4. 4.
    Kawahara K, Moll H, Knirel YA et al. Structural analysis of two glycosphingoliids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata. Eur J Biochem 2000; 267(6):1837–1846.CrossRefPubMedGoogle Scholar
  5. 5.
    Heitman J, G FS, Edwards JEJ, Mitchell AP. Molecular Principles of Fungal Pathogenesis. Washington American Society of Microbiology; 2006.Google Scholar
  6. 6.
    Marr KA. New approaches to invasive fungal infections. Curr Opin Hematol 2003; 10(6):445–450.CrossRefPubMedGoogle Scholar
  7. 7.
    Rapp RP. Changing strategies for the management of invasive fungal infections. Pharmacotherapy 2004; 24(2 Pt 2):4S–28S; quiz 29S–32S.CrossRefPubMedGoogle Scholar
  8. 8.
    McQuiston TJ, Haller C, Del Poeta M. Sphingolipids as targets for microbial infections. Mini Rev Med Chem 2006; 6(6):671–680.CrossRefPubMedGoogle Scholar
  9. 9.
    Rhome R, McQuiston T, Kechichian T et al. Biosynthesis and immunogenicity of glucosylceramide in Cryptococcus neoformans and other human pathogens. Eukaryot Cell 2007; 6(10):1715–1726.CrossRefPubMedGoogle Scholar
  10. 10.
    Matmati N, Hannun YA. Thematic review series: sphingolipids. ISC1 (inositol phosphosphingolipid-phospholipase C), the yeast homologue of neutral sphingomyelinases. J Lipid Res 2008; 49(5):922–928.CrossRefPubMedGoogle Scholar
  11. 11.
    Obeid LM, Okamoto Y, Mao C. Yeast sphingolipids: metabolism and biology. Biochim Biophys Acta 2002; 1585(2–3):163–171.PubMedGoogle Scholar
  12. 12.
    Sims KJ, Spassieva SD, Voit EO, Obeid LM. Yeast sphingolipid metabolism: clues and connections. Biochem Cell Biol 2004; 82(1):45–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Garcia J, Shea J, Alvarez-Vasquez F et al. Mathematical modeling of pathogenicity of Cryptococcus neoformans. Mol Sys Biol 2008; 4:183–195.Google Scholar
  14. 14.
    Rittershaus PC, Kechichian TB, Allegood J et al. Glucosylceramide is an essential regulator of pathogenicity of Cryptococcus neoformans. J Clin Invest 2006; 116(6):1651–1659.CrossRefPubMedGoogle Scholar
  15. 15.
    Casadevall A, Perfect JR. Cryptococcus neoformans. Washington, DC, 381–405: ASM Press; 1998.Google Scholar
  16. 16.
    Luberto C, Toffaletti DL, Wills EA et al. Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans. Genes Dev 2001; 15(2):201–212.CrossRefPubMedGoogle Scholar
  17. 17.
    Shea J, Kechichian TB, Luberto C, Del Poeta M. The cryptococcal enzyme inositol phosphosphingolipid-phospholipase C (Isc1) confers resistance to the antifungal effects of macrophages and promotes fungal dissemination to the central nervous system. Infect Immun 2006; 74(10):5977–5988.CrossRefPubMedGoogle Scholar
  18. 18.
    Heung LJ, Luberto C, Plowden A et al. The sphingolipid pathway regulates protein kinase C 1 (Pkc1) through the formation of diacylglycerol (DAG) in Cryptococcus neoformans. J Biol Chem 2004; 279(20):21144–21153.CrossRefPubMedGoogle Scholar
  19. 19.
    Heung LJ, Kaiser AE, Luberto C, Del Poeta M. The role and mechanism of diacylglycerol-protein kinase C1 signaling in melanogenesis by Cryptococcus neoformans. J Biol Chem 2005; 280(31):28547–28555.CrossRefPubMedGoogle Scholar
  20. 20.
    Gerik KJ, Donlin MJ, Soto CE et al. Cell wall integrity is dependent on the PKC1 signal transduction pathway in Cryptococcus neoformans. Mol Microbiol 2005; 58(2):393–408.CrossRefPubMedGoogle Scholar
  21. 21.
    Luberto C, Martinez-Marino B, Taraskiewicz D et al. Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans. J Clin Invest 2003; 112(7):1080–1094.PubMedGoogle Scholar
  22. 22.
    Mare L, Iatta R, Montagna MT et al. APP1 transcription is regulated by IPC1-DAG pathway and is controlled by ATF2 transcription factor in Cryptococcus neoformans. J Biol Chem 2005; 280(43):36055–36064.CrossRefPubMedGoogle Scholar
  23. 23.
    Tommasino N, Villani M, Qureshi A et al. Atf2 transcription factor binds to the APP1 promoter in Cryptococcus neoformans: stimulatory effect of diacylglycerol. Eukaryot Cell 2008;7(2):294–301.CrossRefPubMedGoogle Scholar
  24. 24.
    Stano P, Williams V, Villani M et al. App1: an antiphagocytic protein that binds to complement receptors 3 and 2. J Immunol 2009; 182(1):84–91.PubMedGoogle Scholar
  25. 25.
    Alvarez FJ, Douglas LM, Rosebrock A et al. The Sur7 protein regulates plasma membrane organization and prevents intracellular cell wall growth in Candida albicans. Mol Biol Cell 2008; 19(12):5214–5225.CrossRefPubMedGoogle Scholar
  26. 26.
    Pasrija R, Panwar SL, Prasad R. Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts. Antimicrob Agents Chemother 2008; 52(2):694–704.CrossRefPubMedGoogle Scholar
  27. 27.
    Oura T, Kajiwara S. Disruption of the sphingolipid Delta8-desaturase gene causes a delay in morphological changes in Candida albicans. Microbiology 2008; 154(Pt 12):3795–3803.CrossRefPubMedGoogle Scholar
  28. 28.
    Ramamoorthy V, Cahoon EB, Thokala M et al. Sphingolipid C-9 methyltransferases are important for growth and virulence but not for sensitivity to antifungal plant defensins in Fusarium graminearum. Eukaryot Cell 2009; 8(2):217–229.CrossRefPubMedGoogle Scholar
  29. 29.
    Kechichian TB, Shea J, Del Poeta M. Depletion of alveolar macrophages decreases the dissemination of a glucosylceramide-deficient mutant of Cryptococcus neoformans in immunodeficient mice. Infect Immun 2007; 75(10):4792–4798.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Departments of Biochemistry and Molecular BiologyMedical University of South CarolinaCharlestonUSA

Personalised recommendations