Intro to Medical Mycology- Kozel Flashcards
What has the most fungal species?
plants
How many common fungal human species are there?
50
Mammals are intrinsically (resistant/suscpetible) to fungus?
Why?
resistant
- they have intact immune systems
- mammalian endothermy
What is mammalian endothermy?
ability to generate and regulate body temp, every 1 degree celcius above 30 degrees kills 6% of fungal species
FUngi emerged as human pathogens only in the (blank).
Why?
1950
Introduction of antibiotics
HIV
immunosuppresive therapies
Is there a high probability for emergence of new pathogens with fungi?
yes
What is the plasma membrane of fungus made out of?
ergosterol
What is the fungal cell wall made out of?
chitin
beta (1,3) glucan
beta (1,6) glucan
Mannoproteins
What kind of mannoprotein is found on Saccharomycetes?
mannan
What kind of mannoprotein is found on Euascomycetes?
galactomannan
Where do you find beta 1-6 glucan? WHere do you find beta 1-3 glucan?
towards the cytoplasm
making a giant X from the outside of the cell wall towards the plasma membrane
What does GPI do?
anchoring protein that fixes the cell wall to the plasma membrane
(blank) is a unicellular fungus that reproduces vegetatively by budding or fission
Yeast
(blank) is a string of budding cells marked by constrictions rather than septa at the junctions.
pseudohyphae
(blank) is a multicellular structure that enlongates at the the tip by apical extension
hyphae
(blank) is a hollow, multinucleate hyphae
Coenocytic hyphae
(blank) is asexual reproductive elements (spores) produced by budding at the top or side of a hyphae
Conidia
(blank) are asexual reproductive elements produced by fragmentation of hyphae
arthroconidia
(blank) are asexual spores produced inside a containg sack-like structure (sporangium)
sporangiospores
What are the four asexual spore?
- Sporangiospores of the Mucorales
- Arthroconidia of Coccidioides immitis
- Conidia of Penicillium spp.
- Conidia of Aspergillus spp.
What are the 5 groups of pathogenic fungi?
Mucormycetes Basidiomycetes Pneumocystidiomycetes Saccharomycetes Euascomycetes
What is the morphology of mucormycetes?
broad, thin-walled hyphae w/ multiple nuclei (coenocytic); septae are rre; sporangiospores
What are the 2 most common mucormycetes?
Rhizopus
Mucor
What is the morphology of Basidiomycetes?
budding yeast, septate hyphae with camp connections and arthroconidia
What are the three most common Basidiomycetes?
Cryptococcus
Malassezia
Trichosporon
What is the morphology of pneumocystidiomycetes?
trophic forms and cystlike structures
What is the most common pneumocystidiomycetes?
pneumocystis jirovecii
What is the morphology of Saccharomycetes?
budding yeast and hyphae, pseudohyphae
What are the 2 most common saccharomycetes?
Candida
Saccharomyces
What is the morphology of Euascomycetes?
budding yeasts, septate hyphae, asexual conidia on specialized structures and arthroconicia
What are the 5 most common Euascomycetes?
Dermatophytes Blastomyces Histoplasma Aspergilus Coccidioides
What are the 6 ways to diagnose fungal infections?
culture direct microscopy histopathology serology molecular methods antigen detection
What is the gold standard in fungal diagnosis and what are its pitfalls?
culture
- requires highly skilled lab tech
- takes days to weeks for results
- often negative for disseminated diseases
Does culturing allow for sensitivity testing?
yes
How do you use a microscope to diagnose fungal infections?
scrapings w/ KOH to digest tissue
use negative stain of CSF for encaspulated cryptococci
How do you use histopathy to diagnose fungal infections?
Cytologic preparations, fine-needle aspirations, body fluids, and exudates.
usually requires invasive sample
What are the routine stains for diagnosis of fungal infection? special stains?
H & E
Gomori methenamine silver, PAS, mucicarmine)
How can serology diagnose fungal infection?
What is its pitfall?
- detects antibody to fungal antigen
- complement fixation or other immunoassay formats
- good for coccidiodomycosis and histoplasmosis
May not reflect active infection; IgM vs. IgG
How can molecular methods diagnose fungal infections?
What are its pitfals?
- Detects nucleic acids via PCR
- Useful for identification of cultured fungi
Problematic for identification in blood or tissue
NO FDA-cleared test
How can antigen detection diagnose fungal infections?
What are the three antigens it works well on?
detects circulating antigens
- cryptococcal antigen (CrAg) very useful for cryptococcosis
- Beta glucan-detects cell wall glucan in blood
- galactomannan-detects histoplasmosis, blastomycosis, coccidioidomycosis
What is an Azole (such as fluconzole)?
antifungal
What is the structure of an Azole?
imidazoles (2 rings)
triazoles (3 rings)
What are the 2 imidazoles of the Azoles family?
Ketoconazole
Miconazole
What are the 3 triazoles of the Azoles family?
fluconazole
itraconazole
voriconazole
What is the MOA of Azoles?
inhibit lanosterol 14-alpha-demathylase
Blocks ergosterol synthesis
How can you get resistance to Azoles?
target with decreased affinity
efflux pump
overexpression of target
What is the clinical use of the Azole Ketoconazole?
limited use due to toxicity and less efficacy
What is the clinical use of the Azole Fluconazoe?
candidiasis, cryptococcosis
What is the clinical use of the Azole Itraconazoe?
broad spectrium antifungal activity
What is the clinical use of the Azole voriconazole?
broad spectrum; invasive aspergillosis
What is the absorption, fate and excretion of Azoles?
great oral absorp
low protein binding
good distribution to organs/tissues including CNS
What is the toxicity and side effects of Azoles?
Fluconazole-low toxicity
Other azoles-variable toxicity
inhibitor of cytochrome p450 so lots of drug interaxns
What is Allylamine?
a antifungal
What are the 2 allylamines?
terbinafine
naftifine
What is the MOA of terbinafine?
inhibition of squalene epoxidase
What is the clinical use of allyamines (terbinafine, naftifine)?
topical treatment of dermatophyte infection
systemic treatment of dermatophyte infection
What is the absorption, fate, toxicity and excretion of allyamines (terbinafine, naftifine)?
well absorbed, rapidly metabolized in liver
high conc. in fatty tissue, skin, hair and nails
well tolerated ORALLY
pregnancy category B.
What is flucytosine and what is its structure?
it is an antifungal and is a prodrug.
How do you activate flucytosine?
deaminate to active 5-fluorouracil in yeast cell
What is the MOA of flucytosine?
antimetabolite-competes with uracil
INHIBITOR of DNA and RNA synthesis
What causes resistance in Flucytosine?
relatively common in monotherapy
decreased uptake
failure to convert to active form
What is the clincal use of Flucytosine?
- used in combination with Amphotericin B
- treatment of cryptococcal meningitis
What is the absorption, fate, and excretion of flucytosine?
taken orally, rapidly absorbed from GI tract.
widely distributed in body, good CNS penetration
Excreted unchanged in urine
What is the toxicity and side effects off flucytosine?
depresses bone marrow
hepatoxicity
What are Echinocandins- caspofungin? What is its structure?
fungal antibiotic
cyclic lipopeptide
What is the MOA of Echinocandins-caspofungin?
inhibits glucan synthesis
How can you get resistance to Echinocandins (caspofungin)?
RARE
in lab- altered target w/ decreased sensitivity
What is the clinical use of Echinocandins- Caspofungin?
used for fungi where 1,3 beta-glucans are the dominant cell wall glucan component
Invasive candidiasis
Invasive aspergillosis
What is the absorption, fate, and excretion of Echinocandins?
administered IV
POOR ORAL
Extensive protein binding
limited CNS penetration
What is the toxicity and side effects of Echinocandins?
generally well tolerated
Pregnancy category C
What are the structures of polyenes?
Amphotericin B
Lipid formulations of AmB
Nystatin
What is the mechanism of action of Polyenes?
binds to ergosterol
DIRECT membrane damage
How can you get resistance to Amphotericin B?
RARE
Mutiple mechanisms: reduced ergosterol content. ergosterol w/ reduce binding, masking of ergosterol to block binding
What is the clinical use of Polyenes (amphotericin B)?
established agent
broad spectrum
lipid formulations less toxic but expensive
What is the absorption, fate, and excretion of amphotericin B?
-Given IV; BECAUSE GI absorption is negligible
(pharm properties differ w/ formulation)
negligible excretion in urine
What happens to conventional AmB?
remains in plasma, largely bound to protein
What happens to Liposomal AmB?
has highest plasma concentration at therapeutic doses
What is the toxicity and side effects of AmB?
considerable nephrotoxicty (azotemia -nitrogen compounds in blood- found in 80% of patients given conventional AmB)
How can you reduce nephrotoxicity w/ AmB?
w/ lipid formulations
The patient is a 70-year-old woman with uncontrolled type 2 diabetes mellitus who presented with a one-month history of non-specific headaches associated with progressive swelling of her left eye. A diagnosis of invasive mucormycosis was made from a tissue biopsy taken from the internasal septum. She was successfully treated with intranasal and systemic amphotericin B. What is the mechanism of action of this antifungal agent?
A) Inhibits lanosterol 14-α-demethylase to block ergosterol synthesis
B) Binds to ergosterol to damage cell membranes
C) Inhibits glucan synthesis
D) Inhibitions squalene epoxidase
E) Inhibits DNA and RNA synthesis
B!!
The government of a country in Southeast Asia instituted prophylactic treatment of all AIDS patients with fluconazole to prevent development of cryptococcal meningitis. Over time, there was no increase in fluconazole resistance by Cryptococcus neoformans, but there was a dramatic increase in the resistance of Candida albicans. What is the most likely mechanism for the increased resistance to fluconazole?
A) An alteration or decrease in the amount of ergosterol in the cell membrane
B) Production of a lanosterol 14 α-demethylase with decreased affinity for the drug
C) Alterations in fungal genes that produce a failure to convert the drug into an active form
D) Alterations in genes that encode proteins involved in glucan synthesis
E) Production of squaline epoxidase with reduced binding to the drug
B.Production of a lanosterol 14 α-demethylase with decreased affinity for the drug. Multiple mechanisms for resistance to fluconazoles have now been identified due to the widespread use of the antifungal. The other major mechanism is production of an efflux pump.
What are the four types of pathogenic fungi?
Superficial mycoses
Cutaneous and subcutaneous mycoses
Endemic Mycoses
Opportunistic mycoses
What are the four endemic mycoses?
Blastomycosis
Histoplasmosis
Coccidiodomycosis
Penicilliosis
What are the five opportunistic mycoses?
Aspergilosis Candidiasis Cryptococcosis Mucormycosis Pneumocystosis
Where will you find superificial mycoses?
superficial skin surfaces of skin and hair
Are superificial mycoses destructive?
no, they are of cosmetic importance
What are the diseases associated with superficial mycoses?
Pityriasis versicolor- Malassezia furfur
Tinea nigra- Hortaw werneckii
Black piedra- Piedraia hortae
White piedra- Trichosporon spp.
What causes pityriasis versicolor?
Malassezia furfur
What causes Tinea nigra?
Hortae werneckii
What causes Black piedra?
Pieraia hortae
What causes White piedra?
Trichosporon spp.
(blank) is infection of keratinized layers of skin, hair and nails
cutaneous mycoses
What is the pathology of cutaneous mycosis due to?
host respose
What are the three cutaneous mycoses?
microsporum spp.
trichophyton spp.
epidermophyton floccosum
What are the diseases associated with cutaneous mycoses?
Dermtophytoses
Tinea Unguium
Onychomycosis
What is dermatophytoses?
infection of the skin
What is tinea unguium?
infection of the toes
What is onychomycosis?
infection of nails
What are subcutaneous mycoses?
infections of deep layers of skin, cornea, muscle and connective tissue
What causes subcutaneous mycoses?
hyaline molds
pigmented fungi
What 2 fungi are hyaline molds?
acremonium spp, fusarium spp.
What 2 fungi are pigmented gunfi?
alternaria spp, Cladosporium spp, exophila spp.
What are the diseases associated with subcutaneous mycoses?
- infection via traumatic inoculation
- abscess formation, nonhealing ulcers, draining sinus tracts
- localized; rarely disseminate
THe same fungus can present in 2 different ways, what is this called?
dimorphism
What are the 2 phases called of fungus?
Saprobic phase (eats dead stuff) and parasitic phase (eats live stuff)
What are the five fungi that present with a saprobic phase and a parasitic phase making them dimorphic?
histoplasma capsulatum blastomyces dermatitidis paracoccidioides brasiliensis coccidioides immitis penicillium marneffei
What is this: dimorphic fungus -parasitic phase (in tissues)-broad based yeast -saprobic phase- non descript mycelium found in decaying organic matter broad based yeast
Blastomyces dermatitidis
Where is blastomyces dermatitidis found?
ohio and mississippi river valleys
What diseases does blastomyces dermatitidis cause?
- pulmonary disease
- extrapulmonary- skin, GU, CNS
- disseminated disease in immunocompromised patient
What is this: dimorphic fungus -in tissues-intracellular budding yeast -saprobic phase-tuberculate macroconidia Found in soil with high nitrogen content-bird/bat droppings
Histoplasma capsulatum
Where is histoplasma capsulatum found?
Ohio and mississippi river valleys, Mexico, central and south america
What are the diseases associated with histoplasma capsulatum?
- acute pulmnary-(90% asymptomatic)
- chronic pulmonary
- progressive disseminated
What is this: Dimorphic fungus -in tissues- endosporulating spherule -saprobic phase- athroconidia Found in soil and dust
Coccidioides immitis/posadasii
Where can you find coccidioides immitis/posadasii?
southwestern U.S., mexico, central and south america.
What are the diseases associated with coccidioides immitis/posadasii?
Primary pulmonary (often asymptomatic)
Progressive pulmonary
Disseminated- usually immunocompromised
What is this:
dimorphic fungus
-tissue-sausage shaped yeast
-saprobic phase- pigmented mold
penicillium marneffei
What are the diseases associated with Penicillium marneffei?
Disseminated infection (more commin in AIDS) Resembles histoplasmosis, cryptococcosis or TB
What is this: Dimorphic fungus -in tissue-large, multiply budding yeast -saprobic phase- nondescript mold Found in soil
Paracoccidiodes brasiliensis
Where do you find paracoccidiodes brasiliensis?
south and central america
What diseases are associated with paracoccidioides brasiliensis?
self-limiting pulmonary disease
progressive pulmonary
disseminated
[more common in children and immunocompromised patient]
A 27-year-old man from Mexico with newly diagnosed AIDS presents to the clinic with 4 weeks of fever, chills, night sweats, myalgias, dry cough, nausea, vomiting, and diarrhea. He recently had a negative tuberculin skin test. He is initially treated for presumptive Pneumocystis pneumonia and atypical pneumonia. Two weeks later, however, fungal blood cultures show growth of hyphal elements shown in the figure. What is the diagnosis?
Disseminated histoplamosis. The figure shows the tuberculate macroconidia of Histoplasma capsulatum when the fungus is grown at room temperature. Tissue or growth at 37°C would show small budding yeast. The fungus is endemic in the Ohio and Mississippi river valleys, Mexico and Central and Southern America
A 71-year-old Chinese male was admitted with complaint of chronic cough, malaise and transient low-grade fever. The patient received a procedure of right middle lobe and lower lobectomy. Histopathology and results of culture at room temperature are shown. It is likely that a travel history would show that the patient had visited the following region of the U.S A) New England B) Florida C) Ohio river valley D) Desert southwest E) Pacific northwest
Desert southwest
The histopathology and culture show, respectively, the spherules and arthoconidia of Coccidioides immitis. C. immitis is endemic in Southwestern U.S., Mexico, and Central and South America.
What is this:
- several species
- ubiquitous in air, soil, decaying matter
- infection by inhalation of spores
- septate, branching hyphae in tissue
Aspergillus spp.
What diseases are associated with aspergillus spp.?
- allergic reactions
- obstructive paranasal or bronchial
- invasive pulmonary and disseminated
Who will get invasive pulmonary and disseminated disease from aspergillus spp?
neutropenic or immunodeficient patient (BMT, solid organ transplant, HIGH FATALITY)
What is this:
- multiple species
- yeast-like forms with buds, pseudohyphae and germ tubes
- normal flora of humans
Candida spp.
What is the most common species of Candida spp.?
C. albicans
What are the diseases associated with Candida spp. ?
Oropharyngeal infection -thrush
Esophagitis - AIDS
Vulvovaginal
Hematogenous disseminated
What is this:
- encapsulated yeast
- ubiquitous saprophyte-pigeons, trees
- immunoassay for capsular antigen
Cryptococcus neoformans
What are the diseases associated with Cryptococcus neoformans?
- pulmonary cryptoccosis
- cryptococcal meningitis
- opportunistic -AIDS or other immune suppresion
- major disease in AIDS in resource-imited countries
What are the 2 species of cryptococcus neoformans?
neoformans and gattii
What is this:
- Mucorales e.g. Mucor and Rhizopus
- Aseptate (coenoytic) hyphae
- Ubiquitous in soil, decaying vegetation
- Acquired by inhalation of spores
Mucormycocis
What diseases are associated mucormycocis?
rhinocerebral
pulmonary
disseminated, angioinvasive
Patient with metabolic acidosis and hematologic malignancy
What are 2 common mucormycocis species?
mucor and rhizopus
What is this:
- sexual and asexual life cycle
- tropic, sporocyst and cyst forms
- cysts seen as empty, collapsed balls
- Human reservoir most likely
Pneumocystis jirovecii
What diseases are associated with Pneumocystis jirovecii?
- Natural resistance very high
- likely infects most normal humans
- AIDS, immunosuppression, infants
- Interstitial plasma cell pneumonitis
- high mortality if untreated
The patient is a homeless 24-year-old male who presents with shortness of breath, fever and a non-productive cough. The patient was diagnosed with AIDS on the basis of CD4 counts and viral load. Examination of induced sputum showed cysts suggestive of Pneumocystis infection. What is the initial source of infection by Pneumocystis jirovecii?
A) An infected animal
B) An infected human
C) Contamination in the domestic water system
D) Water in an air-conditioning cooling tower
E) Contaminated soil
B!!
The reservoir for Pneumocystis jirovecii is not known with certainty. However, given the fact that the microbe is highly adapted to its host, the reservoir is most likely an infected human.
The patient is a 32-year-old male who presents with headache, fever, cranial nerve palsies, memory loss and lethargy over several weeks. A lumbar puncture was done. CSF analysis showed lymphocytic pleocytosis, decreased glucose and slightly elevated protein. A stain of CSF is shown. What is the most likely cause of this patient’s infection?
A. Cryptococcus neoformans B. Mycobacterium tuberculosis B. Nocardia asteroides D. Staphylococcus aureus E. Listeria monocytogenes
A!!!
Cryptococcus neoformans
