Mechanisms of Fungal Pathogenesis Flashcards
PATHOGENESIS OF FUNGAL DISEASE
Capable of initiating infection in a normal, immunocompetent host
Primary pathogens
Able to colonize the host, find a suitable microenvironmental niche withsufficient nutritional substrates, avoid or subvert the normal host defense mechanisms, and then multiply within the microenvironmental niche
Primary pathogens
what pathogen is this?
- Growth at 37C
- Thermal dimorphism
- modulation of yeast-host
- generation of th2 response
- shedding of Bad-1
BLASTOMYCES
DERMATITIDIS
saprobic phase
BLASTOMYCES
DERMATITIDIS
septate mycelium and conidia
parasitic phase
BLASTOMYCES
DERMATITIDIS
large, broad-based, budding yeast
Habitat/Infection of BLASTOMYCES
DERMATITIDIS
soil, organic debris,
endemic area: southeastern US & Ohio-Mississippi river valley
- infection through inhalation of conidia
BAD-1 is
a cell surface glycoprotein
BLASTOMYCES
DERMATITIDIS
clinical syndromes of BLASTOMYCES
DERMATITIDIS
- pulmonary blastomycsis (pneumonia)
- ulcerative/verrucous skin lesions
- osteomyelitis
- prostatitis
- meningitis
- intracranial abscess
Pathogenesis of what fungi?
inhaled conidia convert to yeast; localized yeast invasion of host invokes inflammatory reaction; yeast escapes recognition by macrophages and disseminates via bloodstream
Blastomyces dermatitidis
Promotes adhesion of the yeast cell to macrophages and elicits a potent response of both the humoral and cellular immune systems. BAD1 for what fungi?
Blastomyces dermatitidis
what fungi?
Resistance of conidia to phagocytic killing:
Coccidioides
Saprobic phase of C. immitis consists of septate filamentous hyphae that when mature produce
Coccidioides
barrel-shaped arthroconidia separated form one another by empty disjunctor cells
chinchin
Arthroconidia are very hydrophobic and easily aerosolized. Small enough that when inhaled, ___
Coccidioides
they can be carried deep into respiratory tract to level of alveoli
Saprobic phase:
Coccidioides
septate hyphae and arthroconidia
Parasitic phase:
Coccidioides
spherules with endospores
- Pathogenesis: inhaled arthroconidia reach alveoli; convert to spherule that gives rise to endospores; endospores phagocytosed but survive; large spherules escape phagocytosis; alkaline environment allows survival within phagosome
what fungi?
Coccidioides
what fungi?
urease production
Urease make the alkaline environment especially suitable to survive in the stomach and to grow out in the wild desert
Coccidioides
○ Mimics a estrogen binding protein (progesterone and 17-beta-estradiol)
molecular mimcry
Coccidioides
- Saprobic phase:
HISTOPLASMOSIS
septate hyphae, microconidia, and tubercule macroconidia
Parasitic phase:
HISTOPLASMOSIS
small, intracellular, budding yeast
what fungi?
Pathogenesis:inhaled conidia convert to yeast,
1. yet ingested by macrophages, survive and proliferate within phagosome,
2. some yeast forms remain dormant within macrophage,
3. others proliferate and kill macrophages, releasing daughter cells
HISTOPLASMOSIS
What fungi?
Virulence factors:
* alteration of cell wall composition (1,3-alpha glucans and sphingolipids for antiphagocytic property and oxidative response)
* * growth at 37 degrees C
* thermal dimorphism
* survival in macrophages
* modulate pH of phagosome
* iron and calcium uptake (siderophores and calcium binding protein, CBP1)
HISTOPLASMOSIS
mode of infection
HISTOPLASMOSIS
inhalation of conidia
Clinical diseases:
* clinically asymptomatic pulmonary
* “cryptic dissemination”
* acute pulmonary ____
* mediastinitis and pericarditis,
* chronic pulmonary ____,
* mucocutaneous, disseminated
HISTOPLASMOSIS
what fungi?
- Conversion of inhaled conidia to yeast cells is critical for survival of the pathogen within the host and occurs within hours
○ Would also need a large amount of conidium for infection of immunocompetent person
HISTOPLASMOSIS
what fungi?
Macrophages are the primary host cells in which the yeast phase is important strategy for survival and dissemination of the pathogen
HISTOPLASMOSIS
Dermatophytes:
PATHOGENESIS OF DERMATOPHYTIC FUNGI
Trichophyton, Epidermophyton, and Microsporum
Dermatophytes cause disease in
PATHOGENESIS OF DERMATOPHYTIC FUNGI
humans and/or animals
what kind of fungi?
Invade the skin, hair, or nails
Dermatophytes
Keratinophilic and keratinolytic, Utilizes
PATHOGENESIS OF DERMATOPHYTIC FUNGI
keratinases
DERMATOPHYTIC FUNGI Invade only the upper, outermost layer of the
epidermis (the stratum corneum)
With hair and nails (being part of the skin), only the
DERMATOPHYTIC FUNGI
keratinized layers are invaded
The various forms of dermatophytosis are referred to as
DERMATOPHYTIC FUNGI
“tineas” or “ringworm” infections
tinea capitis of the
scalp, eyebrows, and eyelashes
tinea barbae
of the beard
tinea corporis of the
smooth or glabrous skin
tinea cruris of the
groin
tinea pedis of the
foot
Microsporum produces large
multicellular, thick-and rough-walled macroconidia (most common infection A)
what fungi?
produces microconidia that are teardrop or peg shaped and borne along the sides of hyphae
T rubrum
Trichophyton
what fungi?
produces both single, cigar-shaped macroconidia and grapelike clusters of spherical microconidia D
T mentagrophytes
Trichophyton
what fungi?
produces variably sized and shaped microconidia with relatively large spherical conidia often located right alongside small, parallel-walled conidia and other microconidia of various sizes and shapes [C]
○ T tonsurans
Trichophyton
does not produce microconidia but its smooth-walled macroconidia borne in clusters of two or three are quite distinctive
Epidermophyton
- In hair infections pattern can be and septate hyphae may be seen within the hair shaft in all three patterns:
Ectothrix, endothrix, favic
what dermatophytes does not infect hair?
Epidermophyton
what fungi is associated with this pattern?
Ectothrix: arthroconidia are formed on the outside of the hair
MICROSPORUM
what fungi is associated with this pattern?
Endothrix: arthroconidia are formed inside the hair
TRICHOPHYTON
what is the name of this pattern?
hyphae, arthroconidia, and empty spaces resembling air bubbles (honeycomb patter) are formed inside the hair
Favic:
- Hair infected with M. canis, M. audouinii, and T. schoenleinii often fluoresce yellow-green when exposed to a
Wood light
topical azoles that treat dermatophytic
(azoles): Miconazole, clotrimazole, econazole, tioconazole, and itraconazole
topicals that treats dermatophytic
Terbinafine
Oral antifungals that treat dermatophytic
Griseofulvin, itraconazole, fluconazole, terbinafine
Saprobic phase and parastic:
ASPERGILLOSIS
septate mycelium, conidial heads and conidia
what fungi?
Pathogenesis: inhaled conidia bind to fibrinogen and laminin in alveolus;
* conidia germinate
* hyphal forms secrete proteases and invade epithelium
* vascular invasion results in thrombosis
* infarction of tissue
* hematogenous dissemination
ASPERGILLOSIS
what fungi?
- VF: growth at 37 degrees C, binding to fibrinogen and laminin, secretion of elastase and proteases, catalase, gliotoxin, and other mycotoxins
○ Creates an IgE response which creates those allergy symptoms/diseases
○ Gliotoxin: allow it to evade phagocytosis and inhibits host immune response
ASPERGILLOSIS
mode of infection
ASPERGILLOSIS
inhalation of conidia and transfer to wounds via contaminated tape/bandages
Replication of cryptococcosis is by
CRYPTOCOCCOSIS
budding from a relatively narrow base
what fungi?
Germ tubes, hyphae, and pseudohyphae are usually absent in clinical material
CRYPTOCOCCOSIS
what fungi?
- VF: growth at 37 degrees C, polysaccharide capsule, melanin, alpha-mating type, urease (from pigeon droppings)
○ Alpha-mating type (gender) which produces melanin in capsule
CRYPTOCOCCOSIS
what fungi?
- Pathogenesis: inhaled yeast cells ingested by macrophages; survive intracellularly; capsule inhibits phagocytosis; capsule and melanin protect from oxidative injury; hematogenous and lymphatic dissemination to brain
CRYPTOCOCCOSIS
what fungi?
- Clinical diseases: primary ____ pneumonia, meningitis/meningeal encephalitis, hematogenous dissemination, genitourinary (prostatic) ____, primary cutaneous ____
CRYPTOCOCCOSIS
Most common diagnosis of cryptococcal meningitis is made by
- direct detection of the capsular polysaccharide antigen in serum or CSF (India ink)
Accomplished by using one of several commercially available latex agglutination or enzyme immunoassay kits
what fungi?
Found in environmental niches, food and water, and normal human microbial flora
CRYPTOCOCCOSIS
95% of all candida blood stream infections come from
C. albicans, C. Glabrata, C. parapsilosis, C. tropicalis
CANDIDIASIS
Microscopically
All species exist as oval yeastlike forms that produce buds or blastoconidia
○ Also produce pseudohyphae and true hyphae (no glabrata)
○ Albicans: forms germ tubes and terminal, thick-walled chlamydoconidia (yeast)
may undergo phenotypic switching - where a single strain of candida may change reversibly among several different morphotypes
what fungi?
Candidasis Albicans
Frequency of the switching phenomenon is too high to result from gene mutations and too low to be attributable to mass conversion (all cells in the population change their phenotype in response to signals from the environment
what fungi?
VF: growth at 37 degress C, bud-hyphae transition, adherence, cell-surface hydrophobicity, cell wall mannans, proteases and phospholipases, phenotypic switching
Candidasis
what fungi?
Pathogenesis: mucosal overgrowth with subsequent invasion; usually impaired mucosal barrier; hematogenous dissemination; transfer from hands of health care worker to catheter hub; catheter colonization and hematogenous dissemination
Candidasis
what fungi?
Mode of infection: gastrointestinal translocation, intravascular catheters
Candidasis
Most types of candidiasis represent endogenous infection in which the
normally commensal host flora take advantage of the host’s anti-candida barrier
Candidasis
Clinical diseases: simple mucosa colonization, mucocutaneous ___, oral/vaginal thrush, hematogenous dissemination, hepatosplenic ___, endophthalmitis
Candidasis
what fungi?
Primary site of colonization is the GI tract from mouth to rectum (saprobic habitat)
○ Found as commensals: vagina, urethra, skin, under nails
Candidasis
Albicans can be found in air, water, and soil
what fungi and description
Oropharyngeal infection
○ Mucosal infections = thrush
○ Pseudomembranous type: raw bleeding when scraped
○ Erythematous type: flat, red, and sore areas
○ Leukoplakia: nonremovable white thickening of epithelium caused by candida spp
○ Angular cheilitis: sore fissures at the corners of the mouth
Candidasis
what fungi?
Bronchopulmonary form: asthma, pulmonary infiltrates, peripheral eosinophilia, elevated serum IgE, and evidence of hypersensitivity to ____ antigens (skin test) may be seen
ASPERGILLOSIS
___ can form either in the paranasal sinuses or in a preformed pulmonary cavity secondary to old tuberculosis or other chronic cavitary lung disease
§ May be seen on radiographic examination but are usually asymptomatic
Aspergilloma
ASPERGILLOSIS
form of fungi in the human body?
yeast bc of 37c
risk factor of candida infection
diabetes melitus
