Intro to Fungi Flashcards
What is mycosis?
- a fungal infection in or on part of the body
- a disease caused by a fungus
Fungus: any of numerous ________ organisms in the kingdom Fungi which lack ______ and __________ and range in form from a single cell to a body mass of branched filamentous ________ that often produce specialized ___________. The kingdom includes ______, ______, and ________.
- eukaryotic: have nuclei, usual organelles
- chlorophyll and vascular tissue
- hyphae
- fruiting bodies
- yeasts (unicellular). molds (multicellular) and smuts (fungal disease of flowering plants, and mushrooms)
Discuss fungi cell wall and membrane
- rigid cell wall composed on chitin and glucan, NOT peptidoglycan like bacteria
- cell membrane has ergosterol instead of cholesterol!!
Are bacteria or fungi larger? Who replicates faster?
- fungi
- grow slower than bacteria which follows suite of their size
Describe yeast
- unicellular
- oval shaped or round
- reproduce by budding or fission
Describe molds
- multicellular
- threadlike structures called hyphae** may be separated by septae
- make spores
Describe dimorphic
-exist as mold in nature, but yeast in animals
All fungi can reproduce _________. Give examples.
- asexually
- molds release spores
- yeast undergo binary fission
2 types of hyphae and which lifestyle of mold are hyphae associated with?
- mold
- septated or coenocytic hyphae (hollow and multinucleated)
Where do molds grow or elongate? How do they “spread their seed”?
- at their tips via apical extension
- produce spores (conidia or sporangispores) that are easily airborne and germinate on suitable substrates giving rise to new hyphae
3 common ways to diagnose fungal infections in the lab
- culture of organism: most sensitive but takes time**
- direct microscopic examination: not sensitive, but fast (gram vs. silver stain)***
- Serologic testing for capsular polysaccharide for cryptococcus
* * no molecular tests**
3 targets of antifungal therapy
- cell membrane: ergosterol vs. cholesterol
- DNA synthesis: compounds selectively activated by fungi and arrest DNA synthesis
- Cell wall
2 categories of antifungal drugs that act on cell membrane
- polyene antibiotics
2. azole antifungals
2 drugs that are polyebe antibiotics and what these drugs target
- Amphotericin B
- Nystatin (topical)
* *target fungal cell wall by binding preferentially to ergosterol and forming ion channels that destroy osmotic integrity**
Amphotericin B: activity; fungicidal vs fungistatic; resistance; how it’s administered; side effects; alternative treatments; common uses
- very broad activity, but poor penetration of joints and CNS
- fungicidal since it forms pore
- some resistance seen due to reduced levels of ergosterol in fungal membrane
- administered IV
- Very toxic: nephrotoxicity; fevers, chills, myalgias; hypotension; bronchospasm
- can take lipid formulations that have less side effects but much more expensive
- tends to be used for systemic and opportunistic mycoses
6 azole antifungals and which is most commonly used
- Ketoconazole
- Itraconazole
- Fluconazole**
- Voriconazole
- Miconazole. 6. Clotrimazole (and other topicals)
Compare mechanism of action between polyenes and azoles
-polyenes bind directly to ergosterol while azoles prevent its synthesis (indirect)
Enzyme targeted by azole drugs and what side effects are seen and why?
- azoles bind lanosterol 14a-demethylase inhibiting production of ergosterol
- some cross-reactivity seen with mammalian cytochrome p450 enzymes
- drug interactions and hepatotoxicity: impairment of steroidneogenesis
Are triazoles funastatic or fungicidal?
-fungostatic
2 most commonly prescribed azole drugs and their similarities and differences
-fluconazole and voriconazole
-both can be given orally or via IV, both have good absorption
F: used against Candida, Cryptococcus, Histoplasma, Coccidioides, NOT Aspergillus
V: primary treatment for invasive Aspergillus
Category and drug that act on fungal cell wall
- Echinocandins
- Caspofungin is most important drug
Enzymatic target of Echinocandins; are they fungostatic or fungicidal?
- inhibit B1,3 glucan synthesis (polymer of glucose)
- damage to the cell wall results in osmotic fragility thus they tend to be fungicidal
Caspofungin: how is it administered? What is it used for? Common side effects?
- IV only
- used for invasive candidiasis or invasive aspergillosis refractory to other therapies
- side effects are infusion related: IV site irritation; fever, headache, rash, flushing, erythema due to infusion; symptoms consistent with histamine release–usually not bad enough to be discontinued
Category and drug of antifungal therapy that is DNA synthesis inhibitors
- Pyrimidine analogues
- Flucytosine
Flucytosine: mechanism, resistance, and side effects
- actively transported across fungal membrane where it is converted to 5-flurouracil by cytosine deaminase; further modified and inhibits thymidylate synthase
- resistance arised readily
- side effects with prolonged use: bone marrow suppression, hair loss, abnormal LFTs
Most fungal pathogens do NOT require a host to complete their lifecycles and infections are NOT _______.
-communicable
What are the fungi that naturally inhabit the human body?
- dermatophytes that cause cutaneous infections
- candida sp.
What are true fungal pathogens and what are the 2 examples of them?
- fungi that can cause infection in normal hosts
- they are distributed in a predictable geographical pattern
- Histoplasmosis (Ohio Valley Fever)
- Coccidiomycosis (San Joaquin Valley Fever)
All fungal pathogens, aside from the true pathogens, are _______.
-opportunistic
Pathogenesis of fungi: portals of entry; virulence factors; how our body gets rid of them
- primary mycoses: respiratory portal; inhaled spores
- subcutaneous: innoculated skin; trauma
- Cutaneous and superficial: contamination of skin surface
- VF: thermal dimorphism, toxins, capsules and adhesion factors, hydrolytic enzymes, inflammatory stimulants
- antifungal defenses are integrity of barriers and respiratory cilia
- most important defenses are cell-mediated immunity, phagocytosis, and inflammation
4 different patterns of mycoses infections
- superficial: affect skin, hair, nails; ringwork, jock itch, athlete’s foot
- Subcuteanous mycoses (tropical): affect muscles and CT immediately below skin
- Systemic (invasive) mycoses: involve internal organs; due to primary or opportunistic in immunocompromised
- allergic mycoses: affect lungs or sinuses; patients may have chronic asthma, CF, or sinusitis
2 primary (true) fungal pathogens
- histoplasma capsulatum
- coccidiodes immitis
* both dimorphic*
What causes Histoplasmosis: Ohio Valley Fever? Describe this pathogen.
- Histoplasma capsulatum: most common true fungal pathogen
- dimorphic
- produce conidia (spores) that are inhaled
- ONLY intracellular fungus
Distribution and growing conditions of Histoplasma sp.
- worldwide but most prevalent in eastern and central US
- grows in moist soil high in nitrogen content: associated with bird and bat droppings which have high N2
Histoplasma pathogenesis
- inhalation of spores from disturbed soil
- spores germinate to yeast in lung
- may stay localized or spread via lymphatics within monocytes
- intensity of exposure and immune status are important determinants of pathogenesis
- seen in MACROPHAGES, causes granulomatous inflammation
- reactivation in immunocompromised
What cells is Histoplasma seen in and what type of inflammation does this cause?
- macrophages
- granulomatous inflammation
Clinical Presentations of Histoplasma
- Acute: typically acute, self-limited fu-like syndrome and recover in 1-2 weeks
- rarely progressive pulmonary develops with cavitary fibrosis
- can sometimes cause chronic disease and like TB can remain in lungs and be reactivated later; forms granulomas but unlike TB, are not caseating; diffuse
- disseminated hematogenous spread can present with overwhelming shock, disseminated intravascular coagulation, respiratory distress, and high mortality
Histoplasma lab diagnosis
- microscopic/histologic identification of intracellular yeast
- culture can take 2-3 weeks
- urine antigen to polysaccharide antigen (best if disseminated)
Treatment of Histoplasma
- usually self-limited so don’t treat
- Amphotericin for acute disease
- Long-term Itraconazole for immune compromised, such as AIDS patients
What causes Coccidiomycocis: Valley Fever? Describe the pathology and transmittance of pathogen.
- Coccidiodes immitis
- block-like arthroconidia in the free-living stage and spherules containing endospores in the lungs
- spherules rupture and release spores which starts process again
- arthrospores inhaled from dust, creates spherules and nodules in lung
What environments and regions is Coccidioides found?
- alkaline soils in semiarid, hot climates
- endemic to SW U.S.
Coccidiomycosis symptomatic vs. asymptomatic
- 60% asymptomatic
- reportable disease in CA
- if symptoms, typically self-limited, flu-like
- 1% get disseminated disease
Clinical presentation of Coccidiomycosis
- determined by degree of dust exposure
- Valley Fever is self-limited: 7-21 days after exposure develop cough, fever, joint pain; somtimes get hemoptysis or erythema nodusum (painful nodules on shins); can see eosinophilia
- chest film shows infiltrates with lymphadenopathy; diffuse nodules may be seen and are a more specific finding
- disseminated disease is rare and may involve almost any organ, esp. meninges if untreated
Immunity and Coccidiomycosis
-infection confers immunity and a positive skin test
Coccidiomycosis Diagnosis and treatment
- often missed bc nonspecific symptoms
- Sputum culture (takes weeks, lab hazard)
- Microscopic: look for spherules in tissue/sputum
- self limited infection= no tx
- disseminated disease or patients with risk factors get Amphotericin B plus an Azole, treat with Azole for a year
What is the most important and frequent opportunistic pathogen?
-Candida albicans aka Candidiasis
Morphology of Candida
-yeast, but can form hyphae so not uncommon to see both in clinical specimens
Why is culture of Candida difficult?
-frequently found as normal flora in mouth, gut- makes culture interpretation difficult
Candida is the 4th most common _________. What is its associated mortality?
- bloodstream infection
- 35% mortality
- Candida in the blood is NEVER just a contaminant, always a pathogen
Generally describe the variability of Candida albicans infections
- can be short-lived, superficial skin irritations to overwhelming, fatal systemic diseases involving any organ
- *local or systemic**
Superficial infections due to Candida albicans
- accounts for 80% of nosocomial fungal infections and 30% of deaths from nosocomial infections
- Thrush: thick, white adherent growth on mucous membranes of mouth and throat
- Vulvovaginal yeast infection: painful inflammatory condition of female genital region that causes ulceration and whitish discharge
- Esophageal candidiasis
Risk factors, typical clinical features, and treatment of Candida albicans invasive infections
- RF: immunosuppression, neutropenia, IV catheters, TPN, antibiotics, surgery
- CF: fever (even on Abx), skin lesions, retinitis, endocarditis, microabscesses in any organ
- Tx with Fluconazole or Amphotericin B
How can on tell is abscess is from cancer or infection?
-inflammated, red rim if from infection, not cancer
What causes Cryptococcosis? Describe its morphology
- Cryptococcus neoformans
- widespread encapsulated yeast that inhabits soil and is enriched around pigeon roosts
- oval cells surrounded by halo which is polysaccharide capsule
What patients commonly get Cryptococcosis?
-AIDS, cancer, or diabetes
How is Cryptococcus neoformans transmitted and clinically present?
- organisms is inhaled and amount of inoculum is important
- often relatively asymptomatic or with nonspecific symptoms
- infection of lungs leads to cough, fever, and lung nodules
- can spread via blood to most any organ, but the brain and meninges are favorite targets
What is a favorite target of disseminating Cryptococcus? What are these conditions called?
- brain and meninges
- Cryptococcal meningitis/encephalitis
- can be fatal
Cryptococcal meningitis/encephalitis: who gets it? what are symptoms and outcomes?
- most often in AIDS patients with CD4<50
- high burden or organisms or poor inflammatory response
- indolent meningitis:stiff neck, photophobia uncommon
- initial exam unimpressive, but can progress to mental status changes, visual, hearing, CN findings
- can be chronic, but invariably fatal if not treated
Cryptococcus diagnosis and treatment: what is method of choice?
- direct microscopic examination: india ink preps of CSF
- detection of cryptococcal antigen is method of choice
- systemic infection: Amphotericin B and flucytosine for 2 wks, thenby 8 weeks fluconazole
- AIDS patients can take fluconazole as prophylaxis
What is the method of choice for Cryptococcus and what is it looking for?
-detection of cryptococcal antigen of polysaccharide capsule that breaks off
What is the first opportunistic infection recognized in AIDS patients?
- Pneumocystis pneumonia
- infection only in immunocompromised
What does X ray of Pneumocystic pneumonia look like? What causes it? What life forms does it have? How do you treat it?
- diffuse, bilateral infiltrates; looks more like viral than bacterial pneumonia
- Pneumocystic jiroveci
- trophozoites and cysts
- treat with bactrim
If you stained Pneumocystic with silver stain, what would you see?
-the cysts
Aspergillus is a ubiquitous _________ fungus. It can cause _________.
- airborne soil
- allergic hypersensitivity
Aspergillis morphology
- mold
- acutely branching hyphae with septae with fruiting bodies
Differentiate Aspergillis from Mucor
- A: mold with acutely branching, SEPTATED hyphae with fruiting bodies
- M: mold with NON-SEPTATED hyphae, with right angle branching
Where does Aspergillus infect usually? What if it is invasive?
- usually infects lungs; can colonize sinuses, ear canals, eyelids, and conjunctiva
- invasive: produce necrotic pneumonia and infection of brain, heart, and other organs
Aspergillus spores germinate and form ________. What are these? Why are they a tx obstacle?
- fungal balls/aspergilloma
- noninvasive fungus balls in a cavity
- usually seen with preexisting lung disease like sarcoid or TB
- often asymptomatic, can cause hemoptysis, chest pain, SOB
- drugs are ineffective bc cannot access fungi, so need resection is hemoptysis (expel blood in sputum)
Invasive Aspergillosis
- very destructibe
- angioinvasive, leading to infarction and necrosis
- lung infection is most common but can spread elsewhere
- early diagnosis is essential bc high mortality
How does one diagnose invasive aspergillosis? Treatments?
- tissue needed to visualize fungus bc culture is usually not effective
- Amphotericin and Voriconazole
Cutaneous mycoses are infections strictly confinded to what area and why? What is their common name? Natural reservoirs?
- keratinized epidermis
- fungi feed on keratin
- ring worm
- humans, animals, soil
Cutaneous mycosal infections are facilitated by ____________. They usually have a long infection period followed by?
- moist, chafed skin
- localized inflammation and allergic reactions to fungal proteins
Cutaneous mycoses: infections elicit what response type and what is the result of this? How does one indicate site? KOH preps show what? How does one treat this?
- cellular response leading to inflammed, outward spreading lesions
- Tinea + modifier indicate sites
- branching, septate hyphae seen on KOH preps
- Topical azole antifungals, nystatin
Dermamycoses are caused by fungi that are ______ and _______.
-closely related and morphologically similar
