Chemotherapeutic AgentsFungal Growth PatternsSlide 3Fungal HabitatsMycosisSuperficial MycosesCutaneous MycosisSlide 8Slide 9Subcutaneous MycosesSystemic MycosisSlide 12Slide 13Opportunistic MycosisSlide 15Slide 16Slide 17Differences between fungi and mammalian cellsOverview of Antifungal DrugsAntifungal Drugs - PolyenesAntifungal Drugs - AzolesSlide 22Slide 23Slide 24Antifungal Drugs - AntimetabolitesSlide 26Antifungal Drugs - EchinocandinsAntifungal Drugs - AllylaminesAntifungals - SummaryBIMM118Chemotherapeutic Agents•Antibiotics•Antifungals•Antivirals•Antihelmintics•Antiprotozoal•Anticancer drugsBIMM118Fungal Growth Patterns•Yeasts–Unicellular fungi, reproduce by budding–Moist mucoid or waxy colonies that resemble bacteria•Molds (=Filamentous Fungi)–Multicellular filamentous, “fluffy” colonies consisting of branching tubular structures called hyphae–Collection of intertwined hyphae called mycelium–Vegetative hyphae act like roots, penetrating the supporting medium and absorbing nutrients–Aerial hyphae project above the surface of the mycelium and bear the reproductive structures of the mold (often spread through the air)Candida albicansAspergillusBIMM118Fungal Growth Patterns•Dimorphic Fungi–Grow as molds at ambient environmental temperatures (e.g. 25˚ C) where they form reproductive spore structures. –Spores are aerosolized and infectious –Inhaled spores grow as yeasts at body temperature (37˚ C) in the hostCoccidioides immitisYeast form Mold formBIMM118Fungal Habitats•Most clinically relevant fungi reside in the soil, in bird feces, on vegetation, or on the skin and mucous membranes of mammals. •Some have distinctive ecologic and geographical niches.BIMM118Mycosis•Fungal infections (= mycosis) –spread generally from the environment to people (or animals) with limited person-to-person spread. –Skin and lungs are prominent entry site for many fungi–Patients with impaired cell-mediated immunity (e.g. AIDS, organ transplant) at heightened risk for severe disease. •Types of fungal infections–Superficial: Outer skin layer - no immune responsecaused mostly by yeasts (Dandruff)–Cutenous: Epidermal layers - evoke immune responseTinea (Ringworm, Athlete’s foot, jock itch) caused by Dermatophytes:–Subcutenous: Chronic infection of subdermal tissuesmay require surgical intervention –Systemic: Mostly originating in the lungcaused by virulent dimorphic fungi –Opportunistic: In immunocompromised conditions(AIDS; altered mucosal flora due to antibiotics):mostly Candidiasis and Aspergillosis (often cause of epidemic death in birds)BIMM118Superficial Mycoses•Tinea versicolor (= Pityriasis versicolor)–Caused by a lipophilic yeast, Malassezia furfur –Normal flora of skin and scalp –Growth on media markedly enhanced by adding fat (Clinical mycology labs routinely stock olive oil!) •Dandruff (= Scurf = Pityriasis capitis)–Caused by a lipophilic yeast, Malassezia globosa–Accellerated shedding of skin cellsQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Cutaneous Mycosis–Also known as “ringworm” and tinea (latin “worm”) because of round shape of lesions –Infections confined to skin,hair and nails–Caused by Dermatophyte molds (Trychophytum; Microsporum)Clinical classification based on location:•Tinea capitis–Ringworm of scalp and hair•Tinea barbae–Ringworm of beard regionQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Cutaneous Mycosis•Tinea corporis –Ringworm of the smooth skin of the body•Tinea cruris–Starts in groin area (“Jock itch”)–Causes by Trychophytum rubrumQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Cutaneous Mycosis•Tinea pedis–Classically interdigital (”Athlete’s foot”) –key risk factor for invasive bacterial infections in diabetics through disruption of normal skin barriers•Tinea unguium –Infection of finger and toe nails–Often associated with T. pedisQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Subcutaneous Mycoses•Sporotrichosis–Sporothrix schenckii - Dimorphic fungus –Found on vegetation, especially rose bushes–Introduced into skin by trauma (gardening!) –Initial ulcer develops into granulomatous noduleQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Systemic Mycosis–Infections are rare (high natural immunity)–Usually requires large inoculum–Often endemic to specific aereasMostly associated with four fungi:•Coccidioides immitis -> Coccidioidomycosis–Soil fungus (dry, dusty soil => inhalation of spores)–SW USA (Arizona and Central Valley of CA) and Mexico (“Valley fever”)–Epidemic after (Northridge) earthquake or sandstorms–Considered most virulent fungus(select agent: BSL-3)–Starts with flu-like symptoms, meningitis–Striking racial/ethnic differences in rate of dissemination:Filipinos>African Americans>Hispanics>Asians>Caucasians (Kern County, Filipinos 0.23% of population but 22% of cases) Likely due to genetic differences in blood group/ HLAQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.BIMM118Systemic Mycosis•Histoplasma capsulatum -> Histoplasmosis (“Cave disease”)–Soil fungus (soil containing guano (bird, bat droppings)! => spores inhaled)(In 1890 European starlings were introduced into Central Park, NYC in an effort to bring all of the birds mentioned by Shakespeare to the US => Now there are 200M-1B starlings in N. America, whose droppings are a major route of transmission for histoplasma)–S-SE USA (Ohio and Mississippi Valley) –Starts with flu-like symptoms, meningitis–Fungus lives intracellular in macrophages =>immune-evasion –95% of infected individuals asymptomatic (chronic infection can lead
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