The Production of Eicosanoid Precursors by Mucoralean Fungi

Botha, Alfred; Kock, J.L.F.; Nigam, Santosh

doi:10.1007/978-1-4899-1810-9_48

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…Arachidonic acid-derived eicosanoid production has been reported in nonpathogenic yeasts (3,9,12,13). The nature of the eicosanoids produced by these fungi varies from species to species, and most require exogenous substrates.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic YeastsCryptococcus neoformansandCandida albicansProduce Immunomodulatory Prostaglandins

et al. 2001

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Enhanced prostaglandin production during fungal infection could be an important factor in promoting fungal colonization and chronic infection. Host cells are one source of prostaglandins; however, another potential source of prostaglandins is the fungal pathogen itself. Our objective was to determine if the pathogenic yeasts Cryptococcus neoformans and Candida albicans produce prostaglandins and, if so, to begin to define the role of these bioactive lipids in yeast biology and disease pathogenesis. C. neoformans and C. albicans both secreted prostaglandins de novo or via conversion of exogenous arachidonic acid. Treatment with cyclooxygenase inhibitors dramatically reduced the viability of the yeast and the production of prostaglandins, suggesting that an essential cyclooxygenase like enzyme may be responsible for fungal prostaglandin production. A PGE series lipid was purified from both C. albicans and C. neoformans and was biologically active on both fungal and mammalian cells. Fungal PGE x and synthetic PGE 2 enhanced the yeast-to-hypha transition in C. albicans. Furthermore, in mammalian cells, fungal PGE x down-modulated chemokine production, tumor necrosis factor alpha production, and splenocyte proliferation while up-regulating interleukin 10 production. These are all activities previously documented for mammalian PGE 2 . Thus, eicosanoids are produced by pathogenic fungi, are critical for growth of the fungi, and can modulate host immune functions. The discovery that pathogenic fungi produce and respond to immunomodulatory eicosanoids reveals a virulence mechanism that has potentially great implications for understanding the mechanisms of chronic fungal infection, immune deviation, and fungi as disease cofactors.Prostaglandins are potent regulators of host immune responses. They are produced following the action of a cyclooxygenase on dihomo-␥-linolenic, arachidonic, or eicosanopentaenoic acid (20). The activities of prostaglandins on mammalian cells are numerous. Prostaglandins can inhibit Th1-type immune responses, chemokine production, phagocytosis, and lymphocyte proliferation (1,11,16,18,20,23,26,27). Prostaglandins can also promote Th2-type responses and tissue eosinophilia (4,16,20,24). In the context of anti-fungal immunity, chronic or disseminating fungal infections will result if the Th1-Th2 balance of cellular immunity is shifted away from Th1-toward Th2-type responses (21). The role of prostaglandins in promoting fungal virulence remains to be determined. However, elevated prostaglandin levels have been observed in chronic Candida albicans infections (28). Thus, enhanced prostaglandin production during fungal infection could be an important factor in promoting fungal colonization and chronic infection.Host cells are one source of prostaglandins during fungal infection; however, another potential source of prostaglandins is the fungal pathogen itself. There have been reports in the literature of eicosanoid production by slime molds and soil fungi (12). Our objective was to determine if the pat...

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Section: Discussionmentioning

confidence: 99%

Pathogenic YeastsCryptococcus neoformansandCandida albicansProduce Immunomodulatory Prostaglandins

et al. 2001

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“…However, more reports of arachidonic acidproducing fungi arise as researchers optimize growth conditions. A species of soil fungus, Mucor genevensis, can convert exogenous arachidonic acid to the oxylipin 3-HDTE, which is an 18-carbon species (14,106). In addition, this fungus also produces large quantities of eicosanoid precursors (dihomo-␥-linolenic acid, arachidonic acid, and eicosanopentaenoic acid) when grown under specific conditions.…”

Section: Fungimentioning

confidence: 99%

Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

2003

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Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen “cross-talk” that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens

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“…There are a number of studies that used COX inhibitors, including ASA and other non-steroidal anti-inflammatory drugs (NSAIDs), as well as LOX inhibitors, to identify possible mechanisms involved in fungal eicosanoid production [15,25,36,37], however this has not been able to provide conclusive evidence.…”

Section: Biosynthesis Of Yeast Eicosanoidsmentioning

confidence: 99%

Arachidonic acid metabolites in pathogenic yeasts

et al. 2012

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Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2α and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

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The Production of Eicosanoid Precursors by Mucoralean Fungi

Cited by 5 publications

References 12 publications

Pathogenic YeastsCryptococcus neoformansandCandida albicansProduce Immunomodulatory Prostaglandins

Pathogenic YeastsCryptococcus neoformansandCandida albicansProduce Immunomodulatory Prostaglandins

Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

Arachidonic acid metabolites in pathogenic yeasts

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