Introduction to Fungi Fungal Infections of the Skin and NailsLearning Objectives – Part 1Introduction to FungiPowerPoint PresentationUnique AttributesUnique Attributes are Therapeutic TargetsAntifungal TherapySex in the FungiClassification of FungiThe identification of fungi in the clinical lab is often based on morphology:Slide 11Slide 12Slide 13Learning Objectives – Part IIDermatophyte FungiTinea (Ringworm)TineaSlide 18Athletes and Athlete’s FootPityriasis VersicolorSlide 21Malassezia – host interactionsSeborrheic Dermatitis and Atopic EczemaOnychomycosisSlide 25Systemic MycosesLearning Objective III - Opportunistic Fungal PathogensWHY??A relatively new, susceptible population…..Candida speciesMuco-cutaneous candidiasisDisseminated candidiasis ctd.Slide 33Slide 34Slide 35Slide 36Slide 37ReferencesIntroduction to FungiFungal Infections of the Skin and NailsLearning Objectives – Part 1You should be able to:1. Compare and contrast fungal cell architecture to that of bacterial and mammalian cells.2. Define the major targets for antifungal drugs and explain why they are good targets.3. Explain why antifungal therapies are often toxic to humans.4. Understand basic fungal taxonomy and classifications of the pathogens discussed.5. Appreciate the diversity present within the fungal kingdom6. Appreciate the diversity of fungi present on human skin.Introduction to Fungi•Fungi are eukaryotic organisms–Nucleus, mitochondria (most)–Phospholipid bilayer membrane containing sterols (ergosterol)•Fungi have cell walls that contain chitin and some form of glucan polymer•Fungi are unaffected by antibacterial pharmaceuticalsDOI: 10.1662/0002-7685(2001)063[0164:AUPT]2.0.CO;2Unique AttributesCell Wall Glucan, Chitin and MannoproteinsCell Membrane SterolErgosterolNucleotide MetabolismCytosine DeaminaseUnique Attributes are Therapeutic TargetsCell Wall SynthesisEchinocandinsCell Membrane IntegrityPolyenesErgosterol SynthesisAzolesNucleic Acid Synthesis5-FluorocytosineAntifungal Therapy•Azoles: Inhibit ergosterol biosynthesis–Itraconazole, fluconazole, voriconazole, ketoconazole•Polyenes: Interaction with ergosterol resulting in pore formation and cell leakage–Amphotericin B (gold standard, yet highly toxic)–Liposomal preparations less toxic•Allylamines: Inhibit ergosterol biosynthesis (early)–Terbinafine •Echinocandins: Disrupt cell wall glucan synthesis–Caspofungin•Other: –Selenium sulfide, cyclopirox, griseofulvinSex in the Fungi•Fungi reproduce either asexually or by sexual reproduction. –Asexual reproduction results in progeny that are genetically identical to the parent cell.–Sexual reproduction allows for recombination.•The timing and frequency of sexual reproduction varies among fungal species. •It is thought that sexual reproduction is important for maintenance of pathogenicity.•Sequencing of several loci among clinical isolates in various regions of the world can determine mating frequency.Classification of Fungi•Fungi are generally classified by the type of sexual spore they produceAscomycetes Basidiomycetes ZygomycetesDeuteromycetes produce no sexual spores - imperfect1 1 1The identification of fungi in the clinical lab is often based on morphology:•Colony morphology•Yeast cells, pseudohyphae (chains of elongated yeast cells) or hyphae (long filaments)•For filamentous organism, the shape of the asexual sporulation body•Thermal dimorphism (mold at 25oC, yeast at 37oC)2doi:10.1371/journal.pgen.1000046.g001Fungal Diversity on Skin – Part INature. Jun 20, 2013; 498(7454): 367–370.Fungal Diversity on Skin – Part IINature. Jun 20, 2013; 498(7454): 367–370.Learning Objectives – Part IIYou should be able to:1. Describe the unique characteristics of dematophyte fungi.2. Describe Tinea, and know the common names for tinea infections.3. Describe the unique attributes of Malassezia speices. 4. Describe sebhorreic dermatits and its common names5. Describe onychomychosis.6. Explain why toenail infections are often caused by different organisms than fingernail infections.Dermatophyte FungiTrichophyton rubrumMicroconidia and Macroconidia•Keratinolytic fungi–Can utilize keratin as a nutrient source–Microsporum spp– Epidermophyton spp –Trichophyton spp.Tinea (Ringworm)•Infections of keratinized tissues•Named for location:–Tinea capitis: Scalp–Tinea corporis: Body–Tinea cruris: Groin (jock itch)–Tinea pedis: Foot (athlete’s foot)TineaTinea capitisTinea barbaeTinea corporisTinea crurisTinea unguiumTinea corporisTinea nigraTinea pedis1111111doi:10.3109/1040841X.2013.856853Athletes and Athlete’s FootClin J Sport Med. 2007 Jan;17(1):52-4.Pityriasis Versicolor•Superficial infection of the epidermis–Tan to brown, or non-colored scaly patches primarily on chest and back, but can occur on the extremeties–Conicidence with regions rich in sebaceous glands•Causative Agent: Malassezia spp.–M. furfur , M. globosa and M. sympodialis most common.–Dimorphic, lipophilic fungus–Commensals of the skin–90-100% colonization rates, factors that result in disease unclear–Encode in the genome lipases, sphingomyelinases and phospholipases that aid in infection.•Occurrence: common–Up to 3% of dermatology diagnoses in the summer months in temperate climates–Most often seen in tropical climates (up to 40% prevalence)Treatment:–Topical antifungalsPityriasis VersicolorVolume 31, Issue 4, July–August 2013, Pages 455–463Malassezia – host interactionsVolume 31, Issue 4, July–August 2013, Pages 455–463Seborrheic Dermatitis and Atopic Eczema•Occurs in lipid-rich areas of skin•Red, flaking patches of skin•Some with greasy appearance•Occur frequently in winter months•Dandruff is mildest formOnychomycosis•Fungal infection of the nails–Predisposing factors:•Tinea pedis, family history, age, male gender, trauma, diabetes, immunosuppression, poor peripheral circulation and smoking.–Organisms:•Dermatophytes: Tinea Unguium. Mainly on toenalis–Trichophyton rubrum•Candida albicans, Candida parapsilosis – Mainly fingernails•Treatment–Nail lacquers: ciclopirox and amorolfine.–Oral antifugals - TerbinafineIncidence of cutaneous fungal species from 1999 to 2002. Values represent the incidence of the 5 most common species isolated from finger onychomycosis (A), toe onychomycosis (B), tinea capitis (C), tinea corporis and tinea cruris (D), tinea manuum (E), and tinea pedis (F). Journal of