Mechanisms of Fungal Pathogenesis

Question 1

PATHOGENESIS OF FUNGAL DISEASE

Capable of initiating infection in a normal, immunocompetent host

Answer 1

Primary pathogens

Question 2

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

Answer 2

Primary pathogens

Question 3

what pathogen is this?

• Growth at 37C
• Thermal dimorphism
• modulation of yeast-host
• generation of th2 response
• shedding of Bad-1

Answer 3

BLASTOMYCES
DERMATITIDIS

Question 4

saprobic phase

BLASTOMYCES
DERMATITIDIS

Answer 4

septate mycelium and conidia

Question 5

parasitic phase

BLASTOMYCES
DERMATITIDIS

Answer 5

large, broad-based, budding yeast

Question 6

Habitat/Infection of BLASTOMYCES
DERMATITIDIS

Answer 6

soil, organic debris,
endemic area: southeastern US & Ohio-Mississippi river valley
- infection through inhalation of conidia

Question 7

BAD-1 is

Answer 7

a cell surface glycoprotein

BLASTOMYCES
DERMATITIDIS

Question 8

clinical syndromes of BLASTOMYCES
DERMATITIDIS

Answer 8

• pulmonary blastomycsis (pneumonia)
• ulcerative/verrucous skin lesions
• osteomyelitis
• prostatitis
• meningitis
• intracranial abscess

Question 9

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

Answer 9

Blastomyces dermatitidis

Question 10

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?

Answer 10

Blastomyces dermatitidis

Question 11

what fungi?

Resistance of conidia to phagocytic killing:

Answer 11

Coccidioides

Question 12

Saprobic phase of C. immitis consists of septate filamentous hyphae that when mature produce

Coccidioides

Answer 12

barrel-shaped arthroconidia separated form one another by empty disjunctor cells

chinchin

Question 13

Arthroconidia are very hydrophobic and easily aerosolized. Small enough that when inhaled, ___

Coccidioides

Answer 13

they can be carried deep into respiratory tract to level of alveoli

Question 14

Saprobic phase:

Coccidioides

Answer 14

septate hyphae and arthroconidia

Question 15

Parasitic phase:

Coccidioides

Answer 15

spherules with endospores

Question 16

• 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?

Answer 16

Coccidioides

Question 17

what fungi?

urease production

Answer 17

Urease make the alkaline environment especially suitable to survive in the stomach and to grow out in the wild desert

Coccidioides

Question 18

○ Mimics a estrogen binding protein (progesterone and 17-beta-estradiol)

Answer 18

molecular mimcry

Coccidioides

Question 19

• Saprobic phase:

HISTOPLASMOSIS

Answer 19

septate hyphae, microconidia, and tubercule macroconidia

Question 20

Parasitic phase:

HISTOPLASMOSIS

Answer 20

small, intracellular, budding yeast

Question 20

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

Answer 20

HISTOPLASMOSIS

Question 21

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)

Answer 21

HISTOPLASMOSIS

Question 22

mode of infection

HISTOPLASMOSIS

Answer 22

inhalation of conidia

Question 23

Clinical diseases:
* clinically asymptomatic pulmonary
* “cryptic dissemination”
* acute pulmonary ____
* mediastinitis and pericarditis,
* chronic pulmonary ____,
* mucocutaneous, disseminated

Answer 23

HISTOPLASMOSIS

Question 24

# 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

Answer 24

HISTOPLASMOSIS

Question 25

# what fungi? Macrophages are the primary host cells in which the yeast phase is important strategy for survival and dissemination of the pathogen

Answer 25

HISTOPLASMOSIS

Question 26

Dermatophytes: ## Footnote PATHOGENESIS OF DERMATOPHYTIC FUNGI

Answer 26

Trichophyton, Epidermophyton, and Microsporum

Question 27

Dermatophytes cause disease in ## Footnote PATHOGENESIS OF DERMATOPHYTIC FUNGI

Answer 27

humans and/or animals

Question 28

# what kind of fungi? Invade the skin, hair, or nails

Answer 28

Dermatophytes

Question 29

Keratinophilic and keratinolytic, Utilizes ## Footnote PATHOGENESIS OF DERMATOPHYTIC FUNGI

Answer 29

keratinases

Question 30

DERMATOPHYTIC FUNGI Invade only the upper, outermost layer of the

Answer 30

epidermis (the stratum corneum)

Question 31

With hair and nails (being part of the skin), only the | DERMATOPHYTIC FUNGI

Answer 31

keratinized layers are invaded

Question 32

The various forms of dermatophytosis are referred to as | DERMATOPHYTIC FUNGI

Answer 32

“tineas” or “ringworm” infections

Question 33

tinea capitis of the

Answer 33

scalp, eyebrows, and eyelashes

Question 34

tinea barbae

Answer 34

of the beard

Question 35

tinea corporis of the

Answer 35

smooth or glabrous skin

Question 36

tinea cruris of the

Answer 36

groin

Question 37

tinea pedis of the

Answer 37

foot

Question 38

Microsporum produces large

Answer 38

multicellular, thick-and rough-walled macroconidia (most common infection A)

Question 39

# what fungi? produces microconidia that are teardrop or peg shaped and borne along the sides of hyphae

Answer 39

T rubrum ## Footnote Trichophyton

Question 40

# what fungi? produces both single, cigar-shaped macroconidia and grapelike clusters of spherical microconidia D

Answer 40

T mentagrophytes ## Footnote Trichophyton

Question 41

# 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]

Answer 41

○ T tonsurans ## Footnote Trichophyton

Question 42

does not produce microconidia but its smooth-walled macroconidia borne in clusters of two or three are quite distinctive

Answer 42

Epidermophyton

Question 43

- In hair infections pattern can be and septate hyphae may be seen within the hair shaft in all three patterns:

Answer 43

Ectothrix, endothrix, favic

Question 44

what dermatophytes does not infect hair?

Answer 44

Epidermophyton

Question 45

# what fungi is associated with this pattern? Ectothrix: arthroconidia are formed on the outside of the hair

Answer 45

MICROSPORUM

Question 46

# what fungi is associated with this pattern? Endothrix: arthroconidia are formed inside the hair

Answer 46

TRICHOPHYTON

Question 47

# what is the name of this pattern? hyphae, arthroconidia, and empty spaces resembling air bubbles (honeycomb patter) are formed inside the hair

Answer 47

Favic:

Question 48

- Hair infected with M. canis, M. audouinii, and T. schoenleinii often fluoresce yellow-green when exposed to a

Answer 48

Wood light

Question 49

topical azoles that treat dermatophytic

Answer 49

(azoles): **Miconazole**, **clotrimazole**, econazole, tioconazole, and **itraconazole**

Question 50

topicals that treats dermatophytic

Answer 50

Terbinafine

Question 51

Oral antifungals that treat dermatophytic

Answer 51

Griseofulvin, **itraconazole**, **fluconazole**, **terbinafine**

Question 52

Saprobic phase and parastic: ## Footnote ASPERGILLOSIS

Answer 52

septate mycelium, conidial heads and conidia

Question 53

# 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

Answer 53

ASPERGILLOSIS

Question 54

# 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

Answer 54

ASPERGILLOSIS

Question 55

mode of infection ## Footnote ASPERGILLOSIS

Answer 55

inhalation of conidia and transfer to wounds via contaminated tape/bandages

Question 56

Replication of cryptococcosis is by ## Footnote CRYPTOCOCCOSIS

Answer 56

budding from a relatively narrow base

Question 57

# what fungi? Germ tubes, hyphae, and pseudohyphae are usually absent in clinical material

Answer 57

CRYPTOCOCCOSIS

Question 58

# 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

Answer 58

CRYPTOCOCCOSIS

Question 59

# 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

Answer 59

CRYPTOCOCCOSIS

Question 60

# what fungi? - Clinical diseases: primary ____ pneumonia, meningitis/meningeal encephalitis, hematogenous dissemination, genitourinary (prostatic) ____, primary cutaneous ____

Answer 60

CRYPTOCOCCOSIS

Question 61

Most common diagnosis of cryptococcal meningitis is made by

Answer 61

* 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

Question 62

# what fungi? Found in environmental niches, food and water, and normal human microbial flora

Answer 62

CRYPTOCOCCOSIS

Question 63

95% of all candida blood stream infections come from

Answer 63

C. albicans, C. Glabrata, C. parapsilosis, C. tropicalis

Question 64

# CANDIDIASIS Microscopically

Answer 64

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)

Question 65

may undergo phenotypic switching - where a single strain of candida may change reversibly among several different morphotypes | what fungi?

Answer 65

Candidasis Albicans ## Footnote 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

Question 66

# what fungi? VF: growth at 37 degress C, bud-hyphae transition, adherence, cell-surface hydrophobicity, cell wall mannans, proteases and phospholipases, phenotypic switching

Answer 66

Candidasis

Question 67

# 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

Answer 67

Candidasis

Question 68

# what fungi? Mode of infection: gastrointestinal translocation, intravascular catheters

Answer 68

Candidasis

Question 69

Most types of candidiasis represent endogenous infection in which the

Answer 69

normally commensal host flora take advantage of the host's anti-candida barrier | Candidasis

Question 70

Clinical diseases: simple mucosa colonization, mucocutaneous ___, oral/vaginal thrush, hematogenous dissemination, hepatosplenic ___, endophthalmitis

Answer 70

Candidasis

Question 71

# what fungi? Primary site of colonization is the GI tract from mouth to rectum (saprobic habitat) ○ Found as commensals: vagina, urethra, skin, under nails

Answer 71

Candidasis ## Footnote Albicans can be found in air, water, and soil

Question 72

# what fungi and description Oropharyngeal infection

Answer 72

○ 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

Question 73

# what fungi? Bronchopulmonary form: asthma, pulmonary infiltrates, peripheral eosinophilia, elevated serum IgE, and evidence of hypersensitivity to ____ antigens (skin test) may be seen

Answer 73

ASPERGILLOSIS

Question 74

___ 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

Answer 74

Aspergilloma | ASPERGILLOSIS

Question 75

form of fungi in the human body?

Answer 75

yeast bc of 37c

Question 76

risk factor of candida infection

Answer 76

diabetes melitus