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MEDICALLY IMPORTANT FUNGI
INTRODUCTION
• Fungi are a diverse group of sacrophytic and parasitic eukaryotic organisms• Kingdom: Mycota• Of 100,000 fungal species only 100 have pathogenic potential for
humans, only a few account for clinically important infections• Mycoses : Human Fungal Diseases• Fungal spores may be important as human allergenic agents
INTRODUCTION
MYCOSES• CUTANEOUS: limited to the dermis• SUBCUTANEOUS : when infection penetrates significantly beneath the
skin• SYSTEMIC : when the infection is deep within the body or
disseminated to internal organs
PATHOGENIC FUNGI
TRUE PATHOGENS
OPPORTUNISTICPATHOGENS
TRUE PATHOGENS
Epidermophyton speciesMicrosporum speciesTrichophyton species
Actinomadura maduraeCladosporium
Madurella griseaPhialophora
Sporothrix schenckii
Blastomyces dermatitidis Coccidioides immitis
Histoplasma capsulatumParacoccidioides brasiliensis
Cutaneous infective agents Subcutaneous infective agents
Systemic infective agents
OPPORTUNISTIC PATHOGENS
Absidia corymbiferaAspergillus fumigatus
Candida albicansCrytococcus neoformans
Pneumocystis cariniiRhizomucor pusillus
Rhizopus oryzae (R.arrhizus)
CLASSIFICATION OF FUNGI
CLASSIFICATION OF FUNGI
Depends on :• Characteristic Structures• Habitats• Modes of Growth • Modes of Reproduction
Cell Wall and Membrane
• Composed mainly of chitin rather than peptidoglycan (bacteria)-so unaffected by antibiotics• Chitin: consists of a polymer of N-acetylglucosamine• Fungal Membrane contains ergosterol rather than cholesterol found
in mammalian cells, use in antifungal agents such as amphotericin which binds to ergosterolpores that disrupts membrane function cell death
Cell Membrane
• The imidazole antifungal drugs ( clotrimazole, ketoconazole, miconazole) and the triazole antifungal agents (fluconazole , itraconazole) interact with the C-14 α-demethylase to block demethylation of lansterol to ergosterol, vital component of cell membrane and disruption of it`s synthesis results in death
HABITAT
• All fungi are heterotrophs ( their require some form of organic carbon for growth)• They depend on transport of soluble nutrients across their cell
membrane• To do this they secrete degradative enzymes ( proteases etc) into
their immediate environment, therefore they live on dead organic material• So Natural Habitat : is soil or water containing decaying organic
matter
MODES OF FUNGAL GROWTH
FILAMENTOUSMOLDS
UNICELLULARYEASTS
However there are some dimorphic fungi ( they switch between these Two forms depending on their environment)
Filamentous (mold-like) Fungi• Thallus (vegetitive body) –
mass of threads with many branches resembling cotton ball
• Mass: mycelium• Threads: hyphae, tubular
cells that in some fungi are divided into segments –septate whereas in other fungi the hyphae are uninterrupted by crosswalls-nonseptate
• Grow by branching and tip elongation
YEAST like FUNGI
• These fungi exist as populations of single , unconnected , spheroid cells, not unlike many bacteria, although they are sometimes 10 times larger than a typical bacterial cell• Yeasts reproduce by budding• Some fungal species particularly
those that cause systemic infection exist as dimorphic fungi
REPRODUCTION
SPORULATION
• The principle way in which fungi reproduce and spread within the environment• Fungal spores are metabolically dormant, protected cells, released by
the mycelium in enormous numbers• Borne by the air or water to new sites , where they germinate and
establish new colonies• Spores can be generate sexually or asexually
ASEXUAL SPORULATION
Colour of a particular fungus seen on bread, culture plate is due to theConidia, easly airborne and disseminated
(MITOSIS)
SEXUAL SPORULATIONmeiosis
Relatively rare compared to asexual sporulation, and spore shape often Used as a method of identification
SEXUAL SPORULATIONmeiosis
Relatively rare compared to asexual sporulation, and spore shape often Used as a method of identification
Superficial Mycoses. . . . .. . . .
Superficial Mycoses andDermatophytosis
• Predisposing factors:• humidity• Immunosuppression• Poor hygiene
• Affects the epidermal area with strong affinity to keratin
Superficial MycosesCausative agents:
Malassezia furfurExophiala werneckii
Trichosporon beigelii Piedraia hortae
Malassezia furfur
lipophilic yeast Found as a normal flora on the skinDiseases :
Pityriasis versicolor Pityriasis folliculitis Seborrhoeic dermatitis; Dandruff Systemic infection
Major Clinical Manifestation:
•Hyper- or hypopigmented of the skin.• Lesions are well-demarcated (white, pink
or brownish)• Fawn-colored macules are the most
common presentation Trunk and upper arms Rarely on neck and face
Pityriasis folliculitis
follicular papules and pustules back, chest and upper armssometimes the neck, seldom the face
Itchy and often appear after sun exposure
Seborrhoeic dermatitis
changes in quantity and composition of sebum increase in wax esters shift from triglycerides to shorter
fatty acid chains increase in alkalinity of skin external local factors such as occlusion
Clinical manifestations:
erythema and scaling in areas with a rich supply of sebaceous glands scalp, face, eyebrows, ears and upper
trunk Lesions are covered with greasy scales Itching is common in the scalp
29
Systemic Infection (M. furfur)
common among infants as catheter acquired Intravenous infusions of lipid Pneumonia results from emboli from
the infected IV catheter
Clinical material/Specimen:
• Skin scrapings
• blood
• indwelling catheter tips
Laboratory Diagnosis
1. Direct Microscopy
10% KOH (glycerol w/ Parker ink or Calcofluor white) clusters of thick-walled round
budding yeast-like cells short angular hyphal forms Yeast cells (3-7um)
Laboratory Diagnosis
“Spaghetti and meatballs”
“Spaghetti and meatballs”
GMS
KOH w/ PI
2. Culture For systemic infection Stimulate growth by natural oils or
other fatty substances Sabouraud's dextrose agar or Sheep
blood agar containing Acti-Dione Dixon's agar containing glycerol mono-
oleate36
Laboratory Diagnosis
Malassezia furfur
Colonies of Malassezia furfur on Dixon's agar. A specialized isolation medium containing glycerol-mono-oleate
Microscopic apperances: Broad-based buds The collarettes of the phialides appear
as distinct dark rings separation the mother & daughter cells
currently no commercially available Serology
Laboratory Diagnosis
Management and Treatment:1. topical agent: imidazole
Ketoconazole shampoo
2. Oral treatment : ketoconazole : itraconazole
3. Alternative: zinc pyrithione shampoo• selenium sulfide lotion • propylene glycol 50% in water twice
daily
Helpful Features
• White discoloration of skin or light brown discoloration
• Spaghetti and meatballs
• Oil and FA requirement
Exophiala wernekii
Phaeoannellomyces werneckiiCladosporum werneckii
common saprophytic fungus soil, compost, humus and on wood
Exophiala werneckiiDisease: Tinea nigra
Chronic superficial fungal infection of the palms
brown to black macules (palmar and plantar and other surfaces of the skin)
Well-defined dark patch with irregular margin, 1-5 cm in diameter on palm; “stained appearance”
Tinea nigra
Lesions: non-inflammatory and non-scaling
Both tropics and temperate zonesUsually <20 y/o; > females (3:1)Predisposing factor: excessive sweating
Exophiala werneckii
Clinical Material: Skin scrapings1. Direct Microscopy:
10% KOH and Parker ink; calcofluor white mounts.
2. Culture: Primary isolation media
Sabouraud's dextrose agar
Laboratory Diagnosis
pigmented brown to dark (dematiaceous)septate hyphal elements
2-celled yeast cells
Initially colonies are mucoid, yeast-like and shiny black. (young yeast)
Abundant aerial mycelia and become velvety, dark olivaceous in colour. (mature mould)
Exophiala werneckii
• Serology Not required for diagnosis
Management & Treatment:
Sulfur soap, SSA, azoles Topical treatment
Whitfield's ointment (benzoic acid compound)
Imidazole agent twice a day for 3-4 weeks
49
Piedraia hortae ascomycetous fungus common in Central and South America
and South-East Asia Disease: Black piedra
Chronic fungal infection of the hair shaft mostly affects young adults epidemics in families
Clinical Manifestations: Does not penetrate the hair follicle Scalp hair: rough, sandy Infected hairs: hard black nodules on the
shaft Nodules: hard, fusiform, firmly
attached to hair shaft
Piedraia hortae Black piedra
Clinical Manifestations: Thick part: fungal cells cemented
together Thin part: hyphal elements
Piedraia hortae Black piedra
Black piedra
Clinical Material: hairs with hard black nodules
1. Direct Microscopy: 10% KOH w/ Parker ink; calcofluor white
darkly pigmented nodules: hair shaft Nodules: pigmented center containing
asci
Laboratory Diagnosis
2. Culture:
• primary isolation media Colonies are dark, brown-
black Take about
2-3 weeks to appear
Laboratory Diagnosis
Management and Treament:
shave or cut the hairs short Terbinafine
Dose: 250 mg a day for 6 weeks
Trichosporon beigelii
Worldwide, tropical or subtropical regions More in temperate zones Disease: White piedra
superficial cosmetic fungal infection of the hair shaft
Affects scalp, axilla, facial and genital hair
Trichosporon beigelii White piedra
Clinical Manifestations: common in young adults Nodules: mucilaginous, white, follicles
not affected irregular, soft, white or light brown
nodules firmly adhering to the hairs 1.0 - 1.5 mm in length no pathological changes are elicited
1. Direct Microscopy: • 10% KOH and Parker ink; calcofluor white
Laboratory Diagnosis
2. Culture:
primary isolation media white or yellowish to deep cream
colored smooth, wrinkled, velvety, dull
colonies with a mycelial fringe.
Laboratory Diagnosis
Serological test in not Required
Management and Treatment:
Shave the hairs Topical: imidazole agent
Trichosporon beigelii
B. Dermatophytes(Cutaneous mycoses)
- fungal infections involving the dermis and its appendages
(hair follicles and nails)
oDermatophytosis - "ringworm" disease (mycotic infection) of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes.
oDermatomycosis - more general name for any skin disease caused by a fungus. - invasion of the cutaneous tissues by other fungi.
THE SKIN PLANTS• Etiological agents are called dermatophytes - "skin
plants". Three important anamorphic genera, (i.e., Microsporum, Trichophyton, and Epidermophyton), are involved in ringworm.
• Dermatophytes are keratinophilic - "keratin loving". Keratin is a major protein found in horns, hooves, nails, hair, and skin. • - use keratin as a source of nitrogen• Ringworm - disease called ‘herpes' by the Greeks, and
by the Romans ‘tinea' (which means small insect larvae).
Dermatophytes• Common Causative agents:a. Microsporum
- hair, skin, rarely nails - children, rarely in adults- spontaneous remission
b. Trichophyton - hair, skin & nails- both children & adults- chronic.
c. Epidermophyton - skin, nails, rarely hair- adults, rarely children
Microsporum speciesMicrosporum gypseum
Microsporum canis
TRICHOPHYTON CLASSIFICATION
Epidermophyton speciesEpidermophyton floccosum
Microsporum speciesMicrosporum gypseum
Microsporum canis
Microsporum speciesCommon features:• Colony:• Mycelium: white to buff• Underside: yellow to reddish brown
• Microscopic• attached singly• thick walls & mature forms are echinulate (spiny)• Spindle-shaped macroconidia • Septate hyaline hyphae
Microsporum gypseum complex • Teleomorphs are Arthroderma gypseum and A. incurvatum.
• Produces abundant macroconidia brownish-yellow due to large numbers macroconidia.
• Surface of culture colony often is powdery in appearance.
• Reverse of colony often appears ragged around edges.
• Macroconidia usually have 4-6 septa or crosswalls, up to 40 µm long
• Microconidia are smaller than in M. canis.
• In lactophenol, water is extracted and can cause the macroconidia walls to collapse. This is an artifact due to mounting media. Macroconidia do not form on infected hair!
Microsporum gypseumMicrosporum gypseum
Microsporum canis• Teleomorph is an ascomycete called Arthroderma
otae.
• Macroconidia are abundant, thick-walled with many septa, up to 15. Macroconidia are often hooked or curved at ends.
• Microconidia are small and clavate (club-shaped).
Microsporum canisTeleomorph: Arthroderma otaeMicrosporum canisTeleomorph: Arthroderma otae
TRICHOPHYTON CLASSIFICATION
Infections by Dermatophytes• Severity of ringworm disease depends on (1) strains
or species of fungus involved and (2) sensitivity of the host to a particular pathogenic fungus.
• More severe reactions occur when a dermatophyte crosses non-host lines (e.g., from an animal species to man).
Common Dermatomycoses• Diseases:• Hairy areas:• Tinea capitis Tinea barbae
• Skin:• Tinea corpuris Tinea cruris• Tinea manum Tinea pedis• Tinea fascie Tinea imbricata
• Nail:• Tinea ungium
Dermatophytosis of the skin• Clinical Manifestations:• “ringworm”• Papules to pustules with clear center and active borders
(peripheral pustules and scaling), itchy,circinate and serpiginous with inflammatory, vesicular, enlarging margins
• Differential Diagnosis:• Psoriasis: dry and circinate borders• Ezcema: no clear center
Tinea or “ringworm”: basic lesion
Dermatophytosis (skin and nail)• Tinea fascie (face)• Tinea imbricata (subtype of Tinea corpuris,
concentric layers of lesions)• Tinea cruris (inguinal area)• Tinea pedis (interdigits of the feet)• Tinea manum (interdigits of the hand)• Tinea ungium (fingernails)
Trichophyton species
• The word "trichophyton" literally means "hair plant". • Presence of macroconidia in cultures varies and may not help
in identification of cultures. • Most common species include:
• Trichophyton mentagrophytes • T. rubrum • T. tonsurans • T. verrucosum • T. violaceum • T. schoenleinii • T. ajelloi (rare infects humans).
• ON SKIN: Scrapings from skin and nails cannot distinguish species in this genus.
• ON HAIR: Pattern of infection can help distinguish etiologic or causal agent.
• For Microsporum species - infections on hair lead to a mosaic pattern of arthrospores.
• For Trichophyton species - infections on hair follow one of the 4 patterns.
• Ectothrix - more or less parallel rows of arthrospores produced on surface of hair. • 1. Small-spored ectothrix (arthrospores are < 5 mm in
diameter) - caused by T. mentagrophytes or T. rubrum (rare). Spores are about the same size as those produced by Aspergillus. • 2. Large-spored ectothrix (arthrospores are 5- 10 mm in
diameter) - caused by T. verrucosum. • Endothrix - growth inside hair shaft only! • 3. "Black-dot" endothrix (hair stubs filled with
arthrospores) - caused by T. tonsurans or T. violaceum. • 4. "Favus hair" endothrix (honeycomb pattern of damage seen
on surface of hair shaft) - caused by T. schoenleinii.
Trichophyton species
Common Features:• Colony:
• Mycelia: Cream, buff to brown, granular to wrinkled• Underside: differ (brown to red)
• Microscopic feature• Microconidia; oval- pyriform• attached singly, some in clusters• have smooth walls • Hyaline septate hyphae
• Areas affected: hair, skin and nails
Tinea capitis (head, hair)• Clinical Manifestations:
• Bald patches, moist, itchy, scaly• Papules to pustules• Friable hair
• Differential Dx:• Alopecia: no scaling• Psoriasis: no loss of hair; silvery scaling• Seborrheic dermatitis: diffuse hair loss;• 6-8 months old; pustular
• Other hairy areas:Tinea barbei (beard)
Tinea capitis
Differential Diagnoses:Alopecia areata
Differential Diagnoses:Seborrheic keratosis
Tinea barbei
Tinea fascies
Tinea corporis
Tinea manum (hand)
Tinea pedis (feet)
Tinea unguium
Epidermophyton speciesEpidermophyton floccosum
Epidermophyton floccosum
• Only one pathogenic species in this genus. • Tinea unguium and tinea
cruris are often caused by this fungus.
/
Epidermophyton floccosum•Colony:•Mycelium: yellow – green, “khaki”;
suede, gentle folds; slow grower•Underside: green to brown
Epidermophyton floccosum• Microscopic:• attached in multiples (2 – 4/group)• moderately thick , smooth walls (beaver tails)• Clubbed-shaped, 2 – 5 cell macroconidia• Septate,hyaline hyphae
Chlamydoconidia• Typically present particularly in older culture.
Dermatophytes
Epidermophyton floccosum
• Areas affected: skin and nails• Disease: Tinea cruris or “jock itch”• Often start on the scrotum and spread to the groin as dry, itchy lesions• Source of infection:• Sharing of linens, towels or clothes• Athletes, soldiers, ship crews
Other Forms Superficial Mycoses
KeratomycosisOnychomycosis
Cutaneous candidiasis