Vulvovaginal candidiasis (VVC) is an infection caused by Candida species that affects millions of women every year. Although Candida albicans is the main cause of VVC, the identification of non-Candida albicans Candida (NCAC) species, especially Candida glabrata, as the cause of this infection, appears to be increasing. The development of VVC is usually attributed to the disturbance of the balance between Candida vaginal colonization and host environment by physiological or nonphysiological changes. Several host-related and behavioral risk factors have been proposed as predisposing factors for VVC. Host-related factors include pregnancy, hormone replacement, uncontrolled diabetes, immunosuppression, antibiotics, glucocorticoids use and genetic predispositions. Behavioral risk factors include use of oral contraceptives, intrauterine device, spermicides and condoms and some habits of hygiene, clothing and sexual practices. Despite a growing list of recognized risk factors, much remains to be elucidated as the role of host versus microorganisms, in inducing VVC and its recurrence. Thus, this review provides information about the current state of knowledge on the risk factors that predispose to VVC, also including a revision of the epidemiology and microbiology of VVC, as well as of Candida virulence factors associated with vaginal pathogenicity.
Glycerol and other polyols are used as osmoprotectants by many organisms. Several yeasts and other fungi can take up glycerol by proton symport. To identify genes involved in active glycerol uptake in Saccharomyces cerevisiae we screened a deletion mutant collection comprising 321 genes encoding proteins with 6 or more predicted transmembrane domains for impaired growth on glycerol medium. Deletion of STL1, which encodes a member of the sugar transporter family, eliminates active glycerol transport. Stl1p is present in the plasma membrane in S. cerevisiae during conditions where glycerol symport is functional. Both the Stl1 protein and the active glycerol transport are subject to glucose-induced inactivation, following identical patterns. Furthermore, the Stl1 protein and the glycerol symporter activity are strongly but transiently induced when cells are subjected to osmotic shock. STL1 was heterologously expressed in Schizosaccharomyces pombe, a yeast that does not contain its own active glycerol transport system. In S. pombe, STL1 conferred the ability to take up glycerol against a concentration gradient in a proton motive force-dependent manner. We conclude that the glycerol proton symporter in S. cerevisiae is encoded by STL1. INTRODUCTIONGlycerol, a C 3 polyalcohol, is an important intermediate in energy metabolism in both prokaryotes and eukaryotes. It has long been used for therapeutic and industrial processes. Aspects of glycerol metabolism are also important in biotechnology, e.g., for bio-alcohol production yields or wine smoothness. Essential roles of glycerol in basic biochemical aspects have been extensively studied in several yeasts and fungi. These include biosynthesis of glycerophospholipid and triacylglycerol from glycerol 3-phosphate and dihydroxyacetone phosphate (Kohlwein et al., 1996;Mü llner and Daum, 2004), redox balance (Ansell et al., 1997;Valadi et al., 2004), osmoadaptation (reviewed by Hohmann, 2002, oxidative stress protection (Påhlman et al., 2001), and response to heat shock (Siderius et al., 2000). Responses to elevated temperatures and high osmolarity involve several signaling pathways including the protein kinase C pathway and the HOG pathway, which regulates intracellular levels of glycerol (Hohmann, 2002;Wojda et al., 2003).In cells ranging from mammals (Lang et al., 1998) to archea (Kempf and Bremer, 1998), osmolytes play an important role in the response to osmotic stress caused by low water availability in environments as diverse as poorly irrigated soils or high-sugar musts. In eukaryotic microorganisms like algae or yeasts, polyols, primarily glycerol, act as osmolytes (reviewed by Brown, 1977 andWang et al., 2001). Their production, consumption and retention are consequently tightly regulated and dynamic processes (reviewed by Hohmann, 2002). Magnaporthe grisea (rice blast) a phytopathogenic fungus with a strong impact on world economy, accumulates glycerol, which allows the penetration of the appressorium into the plant host cell (Thines et al., 2000). Glycerol has also...
Saccharomyces cerevisiae Gup1p and its homologue Gup2p, members of the superfamily of membrane-bound O-acyl transferases, were previously associated with glycerol-mediated salt-stress recovery and glycerol symporter activity. Several other phenotypes suggested Gup1p involvement in processes connected with cell structure organization and biogenesis. The gup1Delta mutant is also thermosensitive and exhibits an altered plasma membrane lipid composition. The present work shows that the thermosensitivity is independent of glycerol production and retention. Furthermore, the mutant grows poorly on salt, ethanol and weak carboxylic acids, suggestive of a malfunctioning membrane potential. Additionally, gup1Delta is sensitive to cell wall-perturbing agents, such as Calcofluor white, Zymolyase, lyticase and sodium dodecyl sulphate and exhibits a sedimentation/aggregation phenotype. Quantitative analysis of cell wall components yielded increased contents of chitin and beta-1,3-glucans and lower amounts of mannoproteins. Consistently, scanning electron microscopy showed a strikingly rough surface morphology of the mutant cells. These results suggest that the gup1Delta is affected in cell wall assembly and stability, although the Slt2p/MAP kinase from the PKC pathway was phosphorylated during hypo-osmotic shock to a normal extent. Results emphasize the pleiotropic nature of gup1Delta, and are consistent with a role of Gulp1p in connection with several pathways for cell maintenance and construction/remodelling.
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