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UCSD BIMM 118 - Lecture 17

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BIMM118Chemotherapeutic 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 structurescalled hyphae– Collection of intertwined hyphae called mycelium– Vegetative hyphae act like roots, penetrating the supporting medium and absorbingnutrients– Aerial hyphae project above the surface of the mycelium and bear the reproductivestructures of the mold (often spread through the air)Candida albicansAspergillusBIMM118Fungal Growth Patterns• Dimorphic Fungi– Grow as molds at ambient environmentaltemperatures (e.g. 25˚ C) where they formreproductive spore structures.– Spores are aerosolized and infectious– Inhaled spores grow as yeasts at bodytemperature (37˚ C) in the hostCoccidioides immitisYeast form Mold formBIMM118Fungal Habitats• Most clinically relevant fungi reside in the soil, in bird feces, onvegetation, 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 limitedperson-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 cellsBIMM118Cutaneous Mycosis– Also known as “ringworm” and tinea (latin “worm”) because of round shapeof 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 regionBIMM118Cutaneous Mycosis• Tinea corporis– Ringworm of the smooth skin of the body• Tinea cruris– Starts in groin area (“Jock itch”)– Causes by Trychophytum rubrumBIMM118Cutaneous Mycosis• Tinea pedis– Classically interdigital (”Athlete’s foot”)– key risk factor for invasive bacterialinfections in diabetics through disruptionof normal skin barriers• Tinea unguium– Infection of finger and toe nails– Often associated with T. pedisBIMM118Subcutaneous Mycoses• Sporotrichosis–Sporothrix schenckii - Dimorphic fungus– Found on vegetation, especially rose bushes– Introduced into skin by trauma (gardening!)– Initial ulcer develops into granulomatous noduleBIMM118Systemic 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/ HLABIMM118Systemic 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 ofthe 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 to lung fibrosis)– In immunecompromised patients systemic infection develops =>multiorgan failure, sepsisBIMM118Systemic Mycosis•Blastomyces dermatitides -> Blastomycosis– Soil fungus (=> spores inhaled)– S-SE USA– Predominantly in lung and skin•Paracoccidioides brasiliensis– Soil fungus (=> spores inhaled)– Central and South America (Brazil—death rate up to 1.5/1000)BIMM118Opportunistic Mycosis– Some fungi are commensal (mucosal flora of mouth, gut, vagina etc.)– Usually growth balanced by microorganisms (lactobacilli)– Only a problem in situations of compromised immune responses(AIDS, antibiotics, chemotherapy, radiation, alcoholism, etc.)•Candida albicans -> Candidiasis– Dimorphic fungus BUT also mold at 37˚ C– Also other Candida species– Cutanous candidiasis: mostly in moist skin folds (obese patients):BIMM118Opportunistic Mycosis•Candida albicans -> Candidiasis (cont.)– Oral candidiasis (“Thrush”)• Babies; denture users• Can progress into Candida esophagitis– Vaginal candidiasis (“Yeast infection”)• Does NOT require immune dysfunction• Severe itching/burning• Commonly associated with antibiotica use• Bacterial infection often falsly self-diagnosed as candidiasis(2/3 of self-diagnosed “yeast infections” actually bacterial!)BIMM118Opportunistic Mycosis•Candida albicans -> Candidiasis (cont.)– Systemic candidiasis• Mucocutaneous barriers breached in patients after surgery, burns• Dissemination to kidneys,


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UCSD BIMM 118 - Lecture 17

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