Block C 2 Flashcards
fungal diseases
what is mycosis (plural mycoses)
any infection caused by a fungus/growth of fungus on or in the body
what does it mean for pathogenic fungi to be dimorphic
exists as either yeasts or in filamentous form
what are the 3 major mechanisms that fungi cause disease through
-inappropriate immune responses
-toxins (mycotoxins)
-host infection (mycoses)
what is the most common toxin that aspergillus produces
aflatoxin
what is aflatoxin in relation to birds
carcinogenic
what human diseases does aflatoxin cause
cirrhosis (children are more prone)
asthma
where does superficial mycosis infect
only the surface layer of skin, hair, or nails
how is superficial mycosis treated
topical antifungal creams
liquid aerosols
name of the drugs that treat superficial mycosis
miconazole nitrate
griseofulvin
collective name of fungi that cause superficial mycoses
dermatophytes
what is superficial mycoses caused by
trichophyton spp.
transmission of superficial mycosis
spores
itching and flaking skin
what is subcutaneous mycosis typically caused by
different fungi than superficial infections
how is subcutaneous mycosis often treated
oral administration of azole antifungal agents
2 examples of subcutaneous mycosis
sporotrichosis
chromoblastomycosis
what is sporotrichosis an occupational hazard of
those working in close contact with soil agriculture workers
miners
gardeners
what does chromoblastomycosis typically form
crusty wart like lesions on hand or leg
what is sporotrichosis caused by
the saprophyte
sporothrix schenckii
size of the round conidia in sporothrix schenckii
2 μM in diameter
what does systemic effect
internal organs
where do systemic fungal pathogens normally live
in soil
how do systemic fungal pathogens infect humans
due to inhaling airborne spores
travels from lungs to other organs and skin
why is chemotherapy difficult to treat systemic mycosis
issues with toxicity
who does systemic fungal pathogens primarily affect
the elderly or otherwise immune compromised
why do systemic fungal pathogens typically infect elderly/immune compromised
age - cell mediated immunity declines
immune system impaired- HIV/AIDS
due to the type of people systemic mycosis infects, what can be said about this type of pathogen
opportunistic pathogens
what are opportunistic pathogens
cause disease only in those whose immune defense can no longer fight off the fungi
what is primary fungal disease
healthy individual infected
what is secondary fungal disease
predisposing condition making the individual more susceptible to infections (HIV)
what are the 3 major systemic mycoses in the USA in order in decreasing incidence
histoplamosis
coccidiodomycosis
blastomycosis
what is histoplasmosis caused by
histoplasma capsulatum (dimorphic)
where is histoplasmosis commonly found
rural areas in mid west USA (airborne)
what occurs with the inhaled spores with histoplasmosis
inhaled spores germinate and grow in the lung
what is coccidioidomycosis caused by
coccidioides immitis (dimorphic)
where is coccidioides immitis found
desert regions of the south west USA
when does coccidioides immitis become airborne
when it rains
what is coccidioidomycosis a cause of
pneumonia
what is blastomycosis caused by
blastomyces dermatitidis (dimorphic)
where is blastomycosis endemic to
areas of north america (great lakes)
if left untreated what occurs with blastomycosis
skin lesions
what is paracoccidioidomycosis caused by
paracoccidioides brasiliensis
where is paracoccidioidomycosis primarily found
subtropical disease (south america)
what does paracoccidioidomycosis infect
intially pulmonary
lesions forming on face or other extremities
how is paracoccidioidomycosis treated
azoles
how is paracoccidioidomycosis treated
azoles
what is cryptococcosis caused by
yeast form of cryptococcus neoformans
where can cryptococcosis occur
virtually any organ of the body
-initally pulmonary/wound
where is crytptococcosis often seen
in HIV/AIDs patients
what is candida albicans
dimorphic yeast often present as a minor component of human normal flora
what diseases can candida albicans cause
thrush
to serious infections in immunocompromised individuals
what can be said of candida albicans genome
highly dynamic
chr rearrangements as means of generating genetic diversity
what is pneomocytosis pneumonia often caused by
pnemocytosis jirovecil
examples of the type of people that pneomocytosis infect
chemo patients/AIDS
premature/severly malnourished children
elderly
infants with hyper IgM syndrome
what do antifungals target
ergosterol
what are the 2 main classes of ergosterol inhibitors
polyenes
azoles
what is the mode of action of ergosterol inhibitors
target unique fungal plasma membrane component
3 steps of how ergosterol inhibitors work
bind to ergosterol
destabilising fungal cell membrane
leading to cell death
what are polyenes
a mol with multiple conjugated double bonds
what do polyenes contain at least 3 of
alternating double and single carbon-carbon bonds
mechanism of action of polyenes
bind to sterols in the fungal cell membrane, principally ergosterol
what does the mechanism of action of polyenes place the membrane in
less fluid
more crystalline state
what leaks from the cell leading to cell death with polyenes
small organic mols inc. monovalent ions (K ,NA, H, Cl)
what are the 3 main classes of azoles
imidazoles
triazoles
thiazoles
mode of action of azoles
inhibit the enzyme lanosterol 14 a-demethylase which converts lanosterol to ergosterol
(except for abafungin)
how does depletion of ergosterol in fungal membrane lead to inhibition of fungal growth
depletion disrupts the structure and many functions of fungal membranes
accumulation of toxic sterol intermediates
what are echinocandins
new class of antifungal drugs
mode of action of echinocandins
inhibit the synthesis of glucan in the cell wall
how do echinocandins inhibit synthesis ofglucan in cell wall
via inhibiton of enzyme 1,3-b glucan synthase
what are beta glucans
carbohydrate polymers that are cross linked with other fungal cell wall components
what does the inhibiton that echinocandins prevent
fungal cell wall synthesis
what does depletion of glycan polymers lead to
weakened cell wall and osmotic stress
what is the source of echinocandins
semi synthetic from pnedmocandin
natural cyclic lipopeptide
what are DNA synthesis inhibitors
nucleic acid analogues
mimicking cellular nucleotides
mechanism of action of DNA synthesis inhibitors
inhibit enzymes req for DNA synthesis
difficult as eukaryotic
example of a DNA synthesis inhibitor
flucytosine
target of DNA synthesis inhibitors
candida infections
cryptococcus neoformans
what is flucytosine used in combination with
amphotericin B and/or azole antifungals (fluconazole)
what can minor infections such as candidal cystitis be treated with
flucytosine alone
are DNA synthesis inhibitors synthetic or natural
synthetic
mode of action of mitosis inhibitors
interfering with fungal mitosis
(disruption of microtubule aggregation)
example of a mitosis inhibitor
griseofulvin
is griseofulvin toxic or nontoxic
relatively nontoxic that can be taken orally but passes through the bloodstream to the skin
target of griseofulvin
used to treat number of types of dermatophytoses (ringworm)
