Fungi Flashcards
What are fungal cell walls made from?
Glucans and chitin
(different from bacteria => beta-lactam abx won’t kill fungi)
What major comonent of the fungal cell membrane is different from the mammalian cell membrane?
The sterol
Fungi have ergosterol, mammals have cholesterol
How are fungi different from bacteria?
- Category
- Fungi are eukaryotic
- Bacteria are prokaryotic
- Size
- Fungi are larger (smallest spores = 2-3.5 uM)
- Bacteria = ~1 uM
- Mode of replication
- Fungi = sexual or asexual
- Bacteria = binary fission
- Structure
- Fungi = unicellular (yeast) or multicellular
- Exhibit dimorphism (yeast form or mold form)
- Bacteria = unicellular
- Fungi = unicellular (yeast) or multicellular
- Cell wall
- Fungi = Chitin + mannan and glucan polysaccharide
- Bacteria = Peptidoglycan, LPS
What is dimorphism, in the context of fungi?
Many fungi have multiple forms
- Mold form = hyphae
- Yeast form
- Spore
- Mode of replication and transmission
- Created in the sexual phase
What are the 3 fungal virulence factor categories?
Give examples of each
- Thermotolerance
- Dimorphism may depend on temperature
- Coccidioidomycosis, histoplasmosis, blastomycosis
- Not easily killed by heat
- Dimorphism may depend on temperature
- Exoenzymes
- Proteases, lipases, phospholipases
- Damage barriers, liberate nutrients
- Toxins
- Ex: aflatoxins can be carcinogenic
- Proteases, lipases, phospholipases
- Cell wall components
- Polysaccharide components (mannan and glucan) are highly immunogenic
Which individuals are at an increased risk of mucosal fungal infections?
Anyone with impaired T-cell immunity
(Ex: HIV, SCID, corticosteroid use, transplant rejection medication, very old or very young)
Which individuals are at an increased risk of invasive fungal infections?
Anyone with impaired neutrophils
(Ex: chemotherapy, corticosteroid use)
What clinical scenarios promote fungal disease?
- Environment
- Warm, wet
- Antibiotic use (disrupts natural flora)
- Catheter or prosthetic device
- Immune status
- Immunosuppression
- Transplant anti-rejection therapy
- Chemotherapy
- Corticosteroids
- HIV/AIDS
- Malnutrition
- Very old or very young
- Immunosuppression
- Disease
- HIV/AIDS
- Neutropenia
- Diabetes melitus (ketoacidosis)
What are the 3 major targets of antifungal drugs?
Give examples
All 3 classes basically target the cell wall or cell membrane
- Membrane distruption
- Polyenes: Bind to ergosterol to cause leaks
- Amphotericin B, nystatin
- Polyenes: Bind to ergosterol to cause leaks
- Sterol synthesis inhibitors
- Azoles (Inhibit cytochrome p450)
- Ketoconazole, fluconazole, itraconazole, etc.
- Allylamines (Inhibit squalene epoxidase)
- Terbinafine
- Azoles (Inhibit cytochrome p450)
- Glucan synthesis inhibition
- Echinocandins (inhibit beta-1,3 glucan production)
- Micafungin, caspofungin, anidulafungin)
- Echinocandins (inhibit beta-1,3 glucan production)
What is the only fungal infection that can be treated with an antibiotic?
Which antibiotic?
Pneumocystosis caused by pneumocystis jiroveci
Treat wiht trimethoprim-sulfamethoxazole
(Other anti-fungals will not work)
What are the three phyla of fungi that are pathogenic to humans?
Name a few organisms in each category
- Ascomycetes
- Candida
- Coccidioides
- Blastomyces
- Histoplasma
- Zygomycetes (cause murcormycosis)
- Rhizopus
- Rhizomucor
- Mucor
- Basidiomycetes
- Cryptococcus
- Malassezia
What is kind of drug is amphotericin B?
What is the mechanism?
Amphotericin B is a polyene, used as an anti-fungal
It binds to ergosterol in the cell membrane causing leakage of electrolytes. This leads to loss of membrane potential
What kind of drug is itraconazole?
What is the mechanism of action of itraconazole?
Itraconazole is an Azole, one of the steroid-synthesis inhibiting anti-fungal drugs
Itraconazole (and the other azols) bind to fungal cytochrome p450 to inhibit sterol synthesis
This causes membrane substrates and toxic intermediates to accumulate
Note: potential drug-drug interactions and hepatic toxicity
One of your patients had a liver transplant 1 year ago. He is adherent to his immunosuppression regimin and is tolerating the graft well.
He was recently diagnosed with a case of tinea capitis.
Which agents might be prescribed as treatment?
Which would not be prescribed?
Most of the antifungal agents will work
Allylamine such as terbinafine may be prescribed
Azoles would not be recommended due to risk of hepatic toxicity (Azoles inhibit cytochrome p405)
What is the mechanism of action of Allyamines?
Allyamines are anti-fungal drugs that work via sterol synthesis inhibition
Specifically, the inhibit squalene epoxidase (an earlier step in sterol synthesis)
What are echinocandins?
What is their mechanism of action?
Echinocandins are anti-fungal drugs that inhibit glucan synthesis
They inhibit beta-1,3 glucan production, which impairs cell wall stress tolerance
Give an example of a superficial mycosis
Which organism is likely to cause this?
Pityriasis versicolor
Malassezia furfur
Describe the clinical presentation of a Malassezia furfur infection
Hypo or hyper pigmented regions only affecting the stratum corneum
Give an example of a cutaneous mycosis
Which organisms are most likely to cause this?
Tinea captis, Tinea pedis, Tinea cruris, Tinea manus
Most likely caused by Dermatophytes
(Ex: Trichopyton, microsporum, epidermophyton)
Describe the clinical presentaiton of an infection by a dermatophyte such as epidermophyton
Invasion of superficial keratinized tissue (skin, hair, nails)
- The tissue will likely be inflamed
- Distant manifestations may be caused by a delayed hypersensitivity reaction
- Systemic infections possile in immunocompomised hosts
How is tinea captis spread?
Tinea captis and other cutaneous mycoses caused by dermatophytes are spred via direct contact
- Group settings
- Skin injury
- Favorable growth conditions
- Immunodeficiency
Give an example of a subcutaneous mycosis
What organism might cause this?
Sporotrichosis
Caused by Sporothrix schenkii
Describe the clinical presentation of a Sporothrix schenkii infection
Subcutaneous mycosis
- Penetrates epethilial layers, but typically remains localized in the subcutaneous tissue
- Granulomatous lesions may spread slowly through the lymphatics
- Systemic infections possible in immunocompromised hosts
How is Sporothrix schenkii spread?
Contaminated objectst that penetrate the skin
Which organisms can cause endemic mycosis?
What infections do they cause?
- Coccidioides immitis -> Coccidioidomycosis
- Histoplasma capsulatum -> Histoplasmosis
- Blastomyces dermatitidis -> Blastomycosis
Describe the clinical presentation of coccidioidomycosis
How is it different from the other endemic mycoses?
- Mild pulmonary infection
- May be subclinical
- Severe pulmonary infection in an immunocompromised host
Less likely to disseminate than other endemic mycosis
Endemic to the Southern USA and Latin America
Which fungal infections are most common in healthy people?
How are they spread?
Endemic mycoses; usually cause pulmonary infection in healthy individuals
- Coccidioidomycosis
- Histoplasmosis
- Blastomycosis
Spread via spore inhalation (no person-person transmission)
Describe the clinical presentation of histoplasmosis
How is it different from the other endemic mycosis?
- Pulmonary infection that replicates in macrophages
- May cause acute pulmonary disease if exposure is high
- May form caseating or non-caseating granulomas
- May look like M**ycobacterium tuberculosis
- May disseminate to RES organs
- More likely in immunocompromised host
More likely to disseminate than coccidiodomycosis
Forms granulomas
Less likely to involve CNS than blastomycosis
Endemic to central and eastern USA
Describe the clinical presentation of blastomycosis
How is it different from the other endemic mycosis?
- Pulmonary infection
- Lower respiratory
- May spread to CNS, gonadal tissues, bone
Look for broad-based budding yeast
More likely to involve CNS than coccidioidomycosis or histoplasmosis
Does not form granulomas like histoplasmosis
Endemic to North America, Canada, Africa, South America, Asia
What similarities do all of the endemic mycoses share?
(Coccidioidomycosis, histoplasmosis, blastomycosis)
- Thermally dimorphic
- Transmission via inhalation of spores
- No person-person transmission
- Can infect healthy people
- But infections more severe in immunocompromised
You see broad-based budding yeast in a patient sample.
Which organism is likely causing this?
Blastomycosis
What similarities do all of the opportunistic mycoses share?
(Candidiasis, cryptococcosis, aspergillosis, murcormycosis, pneumocystosis)
- Marginal pathogenicity
- Usually co-exist with the host
- Cause infection when…
- The host is immunosuppressed
- The bacterial niche is altered (ex: antibiotics)
Which organisms can cause opportunistic mycoses?
What infections do they cause?
-
Candida spp -> Candidiasis
- C. albicans, C. glabrata, C. parapsilosis, C. tropicalis
- Cryptococcus neoformans -> Cryptococcosis
- Aspergillus fumigatus -> Aspergillosis
-
Zygomycosis spp -> Murcormycosis
- Z. rhizopus, Z. rhizomucor, Z. mucor
- Pneumocystis jiroveci -> pneumocystosis
Describe the clinical presentation of Candidiasis
How is it different from the other opportunistic mycoses?
Typically only find in its yeast form; look for white patches on mucosal surfaces
- Colonizes the mucosal surface following trauma or unchecked proliferation (due to antibiotics)
- 3 kinds
- Superficial (mucosal + cutaneous)
- Thrush
- Vulvovaginitis
- Chronic (mucocutaneous)
- Results from childhood immunodeficiency
- Systemic
- Heart
- Kidneys
- Eyes
- CNS
- Superficial (mucosal + cutaneous)
More likely to appear on only mucosal surfaces than other opportunistic mycoses; characterisitc white patches
Describe the clinical presentation of cryptococcosis
How is it different from the other opportunisitic mycoses?
- Pulmonary infection
- Asymptomatic or flu-like
- May spread to CNS
- Chronic meningoencephalitis
- Polysaccharide capsule fragments and causes problems durign treatment; must monitor intracerebral pressure
- Chronic meningoencephalitis
- History of interaction with pigeon guano
Only one found in pigeon guano; can cause seriosus CNS effects
Describe the clinical presentation of aspergillosis
How is it different from the other opportunisitic mycoses?
- Hypersensitivity reaction
- Allergic bronchopulonary aspergillosis
- Recurrent asthma
- Peripheral eosinophilia
- Allergic bronchopulonary aspergillosis
- Pulmonary invasion
- Causes invasive hyphae
- Macrophages control the infection
- Except in immunosuppressed hosts
- May form aspergillomas (similar to granulomas)
Always in mold (Hyphae) form
Look for acute angle growth (45 degrees)
Describe the clinical presentation of murcormycosis
How is it different from the other opportunisitic mycoses?
- Highly invasive local tissue infections
- May spread to CNS
- Thrombosis, infarction
More invasive tissue involvement than other opportunistic mycoses
High risk in Diabetes Melitus patients
Look for 90 degree angle growth of hyphae
Treatment may require surgery
Describe the clinical presentation of pneumocystosis
How is it different from the other opportunisitic mycoses?
- Only causes infection in immunocompromised
- Pneumocystis jiroveci is a commensal of the lung
- Seen especially in premature or malnourished infants and HIV/AIDs patients
- Grows on surfactant of alveolus
- Increases barrer to gas exchange
The only fungal infection that is treated with trimethoprim-sulfamethoxazole (the antifungals don’t work)
Which methods would you use to determine whether a lwoer respiratory tract infection is bacterial or fungal?
- Growth pattern on culture
- Gram stain
- Fungus will not stain
- KOH scrape (to confirm fungus)
- History/exposure
- Lung imaging
- Measure cell wall products in the blood
- Antigen assay
- Lack of response to antibiotic therapy
What is likely causing this infection?
Malassezia furfur
This is a superficial mycoses infection (pityriasis versicolor)
What is likely causing this infection?
A dermatophyte (Trichophyton, microsporum, epidermophyton)
Cutaneous mycoses - tinea corporis
What is likely causing this infection?
Sporothris schenkii
Subcutaneous mycoses - Sporotrichosis
Nodular lesions with lymphatic spread
Which organism is shown in this picture?
Blastomyces dermatidis
(look for broad-based budding yeast)
Which organism exhibits this characteristic pattern:
- Enter the cell and remodel into spherical cells
- Endospores divide
- Rupture and release endospores into tissue
Coccidioidomycosis
Which organism is this?
Coccidiodes
- Enter the cell and remodel into spherical cells
- Endospores divide
- Rupture and release endospores into tissue
Assume that the white patches would scrape off of you tried
What organism is causing this?
One of the Candidia spp
This mucosal infection is associated with T-cell dysfunction (invasive is associated with neutrophils)
Which organism exhibits this pattern of hypae grwoth?
Aspergillus spp.
Lookd for septate hyphae and acut angle branching
Which fungal infection would require close monitoring of intracerebral pressure during treatment? Why?
Cryptococcosis (Cryptococcus neoformans)
The fungus is assosiated with meningoencephalitis. The polysaccharide capsule fragments into bits during treatment and can cause stick together, causing an increase in intracerebral pressure.
A 28-year-old white female presented with a recent-onset rash that involved the upper arms. She was otherwise healthy, with no known allergies and no history of medication or chemical exposure. Physical examination reveals multiple, discrete, 1- to 4-cm, salmon-colored, round, slightly scaly patches on both arms. There was no evidence of lymphadenopathy. What is the cause of her rash?
Malassezia furfur
A 37 year-old male presents with burning in his mouth; on exam he has white plaques over his palate. What is the likely cause of this condition?
Candida albicans
What is the mechanism of fluconazole?
Disrupts the cell membrane by inhibiting ergosterol synthesis
(Same mechanism as all -azoles)
Which fungi are thermally dimorphic?
- Coccidioides immitis*
- Histoplasma capsulatum*
- Blastomyces dermatitidis*
A 57 year-old man presents with pneumonia worsens despite treatment with empiric antibacterial antibiotics (ceftriaxone plus azithromycin). Bronchoscopy shows broad-based budding yeast. What is the likely cause of his pneumonia?
Blastomyces dermatitidis
Blastomyces = broad based budding yeast
