Acetylsalicylic acid as antifungal in Eremothecium and other yeasts

Abstract

Interesting distribution patterns of acetylsalicylic acid (ASA, aspirin) sensitive 3-hydroxy (OH) oxylipins were previously reported in some representatives of the yeast genus Eremothecium--an important group of plant pathogens. Using immunofluorescence microscopy and 3-OH oxylipin specific antibodies in this study, we were able to map the presence of these compounds also in other Eremothecium species. In Eremothecium cymbalariae, these oxylipins were found to cover mostly the spiky tips of narrowly triangular ascospores while in Eremothecium gossypii, oxylipins covered the whole spindle-shaped ascospore with terminal appendages. The presence of these oxylipins was confirmed by chemical analysis. When ASA, a 3-OH oxylipin inhibitor, was added to these yeasts in increasing concentrations, the sexual stage was found to be the most sensitive. Our results suggest that 3-OH oxylipins, produced by mitochondria through incomplete beta-oxidation, are associated with the development of the sexual stages in both yeasts. Strikingly, preliminary studies on yeast growth suggest that yeasts, characterized by mainly an aerobic respiration rather than a fermentative pathway, are more sensitive to ASA than yeasts characterized by both pathways. These data further support the role of mitochondria in sexual as well as asexual reproduction of yeasts and its role to serve as a target for ASA antifungal action.

Oxylipin studies expose aspirin as antifungal

“…Also, when aspirin was added to Ascoidea, the sexual stage proved to be most susceptible to inhibition (Ncango et al, 2007), similar to what was found for Dipodascopsis Kock et al, 1998), Dipodascus (Van Heerden et al, 2007) and Eremothecium (Leeuw et al, 2007). This is to be expected, as aspirin is known to inhibit b-oxidation in mammalian mitochondria and therefore also 3-OH oxylipin synthesis (Glasgow et al, 1999).…”

“…This has been suggested recently (Leeuw et al, 2007) by growth experiments with several yeasts with both energy generation options, such as the aspirin-sensitive, nonfermentative Asc. This has been suggested recently (Leeuw et al, 2007) by growth experiments with several yeasts with both energy generation options, such as the aspirin-sensitive, nonfermentative Asc.…”

“…3-OH oxylipins are widely distributed in yeasts (Kock et al, 1998(Kock et al, , 2003Noverr et al, 2003;Leeuw et al, 2007). Antibodies directed against chemically synthesized 3-OH oxylipins, and found to be specific for 3-OH oxylipins in general, were of assistance in mapping 3-OH oxylipins with different chain lengths and desaturation levels.…”

“…2) (Kock et al, 1998), Dipodascus (Van Heerden et al, 2005, many lipomycetaceous species, i.e. Lipomyces doorenjongii, L. kockii, L. kononenkoae, L. starkeyi, L. yamadae, L. yarrowii, Smithiozyma japonica and Zygozyma oligophaga (Smith et al, 2000b), Saturnispora saitoi , Saccharomycopsis (Sebolai et al, , 2004(Sebolai et al, , 2005, Eremothecium Kock et al, 2004;Leeuw et al, 2006Leeuw et al, , 2007, and Ascoidea (Figs 3 and 4) (Ncango et al, 2006). Although 3-OH oxylipins were reported in lipomycetaceous yeasts, no 3-HETE could be detected when these yeasts were fed with AA .…”

Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases

“…LDH measurements similarly demonstrated that 1 mM ASA reduced RHO cell injury after challenge with Candida . Although antifungal properties have been attributed to ASA in other studies [16-18, 25], its protective capabilities in an infection model have not been previously documented.…”