[Structural and biochemical characteristics of pathogenic fungus: cell walls, lipids and dimorphism, and action modes of antifungal agents].
Cell walls (0.1-0.5 microm in thickness) of dermatophytes, at least Trichophyton mentagrophytes and Epidermophyton floccosum, are built of microfibrils (20 nm in diameter) and matrix embedding the fibrils. These fibrils are composed of chitin (70-80%) and a small amount of glucans, and the matrix is composed of beta-1-3, beta1-6 glucan, glucomannan, galactomannan and peptides. Another characteristic structure is the outermost layer (20-50 nm in thickness) of the cell wall, which consists of hydrophobic protein rodlets. Lipids are thought to play important roles in the regulation of dimorphism and virulence in pathogenic fungus. Generally, the ratio of phospholipid/ergosterol is less than 1 in yeast form and 2-20 in mycelial form cells in Candida albicans and Sporothrix schenckii. During the transition from yeast to mycelial forms, phosphatidylinositol and phosphatidylserine are reduced, whereas phosphatidylcholine increases. Phospho-lipase D is activated on this transition. Phospholipase B is now known to be a virulence factor in C. albicans. Polyene antifungal agents bind to ergosterol in membrane to form complexes, which generate pores and destroy the structures and functions of membrane. Azole antifungal agents inhibit the synthesis of ergosterol leading to deficiency in ergosterol content in membrane, and impair the function of membranes in fungal cells. We show the effects of polyenes on the ultrastructure of fungal plasma membrane and impairment of ionomycin-induced calcium influx in T. mentagrophytes, so that we can compare the differences in mode of actions between these two groups of agents.
Kitajma
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Department of Dermatology, Gifu University School of Medicine, Tsukasamachi 40, Gifu City 500-8705, Japan.
D000935:Antifungal Agents / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000166:cytology* / Q000187:drug effects / Q000472:pathogenicity; D001393:Azoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002686:Chitin / Q000378:metabolism; D004875:Ergosterol / Q000096:biosynthesis / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D008245:Lysophospholipase / Q000378:metabolism / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism / Q000502:physiology*; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology*; D014774:Virulence
D000935:Antifungal Agents; D001393:Azoles; D005936:Glucans; D008563:Membrane Lipids; D011090:Polyenes; D002686:Chitin; D008245:Lysophospholipase; D002118:Calcium; D004875:Ergosterol