Update on Candida krusei, a potential multidrug-resistant pathogen.

Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

Synthesis and function of fatty acids and oxylipins, with a focus on Caenorhabditis elegans.

Polyunsaturated fatty acids (PUFAs) exhibit a diverse range of important biological functions in most biological systems. These PUFAs can be oxygenated via enzymatic or free radical-mediated reactions to form bioactive oxygenated lipid mediators termed oxylipins. Eicosanoids are broad class of oxylipins that are transient and locally synthesized signalling molecules, including prostaglandins, leukotrienes, lipoxins and thromboxanes, which mediate various physiological responses, such as inflammation. In addition to arachidonic acid-derived eicosanoids, current developments in lipidomic methodologies have brought attention to vast number of oxylipins produced from other PUFAs, including omega-3. Although, the molecular mechanisms of how PUFAs and oxylipins contribute to majority of the fundamental biological processes are largely unclear, a model organism Caenorhabditis elegans remains a powerful model for exploring lipid metabolism and functions of PUFAs and oxylipins. For instance, the ability of C. elegans to modify fatty acid composition with dietary supplementation and genetic manipulation enables the dissection of the roles of omega-3 and omega-6 PUFAs in many biological processes that include aging, reproduction, and neurobiology. However, much remains to be elucidated concerning the roles of oxylipins, but thus far, C. elegans is well-known for the synthesis of vast set of cytochrome (CYP) eicosanoids. These CYP eicosanoids are extremely susceptible to changes in the relative bioavailability of the different PUFAs, thus providing a better insight into complex mechanisms connecting essential dietary fatty acids to various biological processes. Therefore, this review provides an overview of the synthesis and function of PUFAs and oxylipins in mammals. It also focusses on what is known regarding the production of PUFAs and oxylipins in C. elegans and their functions.

Acetylsalicylic acid as antifungal in Eremothecium and other yeasts.

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 covered ascospores of Eremothecium coryli.

Eremothecium coryli is known to produce intriguing spindle-shaped ascospores with long and thin whip-like appendages. Here, ultra structural studies using scanning electron microscopy, indicate that these appendages serve to coil around themselves and around ascospores causing spore aggregation. Furthermore, using immunofluorescence confocal laser scanning microscopy it was found that hydrophobic 3-hydroxy oxylipins cover the surfaces of these ascospores. Using gas chromatography-mass spectrometry, only the oxylipin 3-hydroxy 9:1 (a monounsaturated fatty acid containing a hydroxyl group on carbon 3) could be identified. Sequential digital imaging suggests that oxylipin-coated spindle-shaped ascospores are released from enclosed asci probably by protruding through an already disintegrating ascus wall.