Lecture 8 - Mycology Flashcards
6 characteristics of human pathogenic fungi?
- Eukaryotic
- Multiple growth forms: unicellular (yeast), filamentous (molds), or a hybrid between the 2 (pseudohyphae)
- Unique cell wall: structure, protection, antigenic, host cell recognition
- Plasma membrane contains ergosterol, which is one of the anti-fungal drug targets
- Disease transmission: pathogens are acquired from the environment or are part of the normal microbiota of people, i.e., colonize and persist on mucosal surfaces (e.g. Candida)
- Spore production: serve as their infectious agent to infect (e.g aerosols via inhalation), germinate, and grow as filaments called hyphae
Implication for treatment that human pathogenic fungi are eukaryotic?
Toxicity is a problem with some antifungal drugs (e.g. Amphotericin B against ergosterol bind cholesterol in human plasma membranes)
How many diseases caused by human fungi?
~150
What are sporangia?
Sac like structures containing thousands of spores
What does it mean for certain fungal infections to be endemic?
Found only in certain parts of the world
3 types of protective immunity to fungal infections? Examples of fungal infections for each?
- Innate: first line of protection with neutrophils (causing neutropenia = reduced neutrophils) => invasive candidiasis and aspergillosis
- T cells (CD4 and CD8) => mucosal candidiasis (where T cells are less numerous and no extensive oral lesions), cryptococcosis, and histoplasmosis (all common in HIV/AIDS)
- B cells and antibodies (rare) => cryptococcosis
Why are patients who are about to receive a transplant at risk of acquiring a fungal infection?
Because of the induced neutropenia due to immunosuppressants
3 types of anti-fungal drugs and their targets?
- Echinocandins: target beta-glucan, a precursor to glucan, which is a polysaccharide in the cell wall
- Azoles: inhibit sterol synthesis, which is found in cell membranes
- Polyenes: disrupt cell membrane by targeting sterols preventing normal transport
Example of an azole drug?
Fluconazole
Example of a polyene drug?
Amphotericin B
What are 4 problems with anti-fungal drugs?
- Lack of variety of drugs
- Increasing resistance especially among species of Candida (azoles and echinocandins)
- Echinocandins are not broad-spectrum (only work on certain fungi)
- Drug toxicity: which includes both polyenes (binding to cholesterol in human cells) and drug-drug interactions (esp. with azoles)
Describe the mechanisms of resistant to azole anti-fungal drugs. What to note?
- Fungal cells have protein pumps or efflux pumps in their membranes called CDRs and MDRs, whih are responsible for pumping out the antifungal drug before it can act on Erg-11 in the ergosterol synthesis pathway => number of these pumps determines if the fungal cell will be susceptible or resistant to an azole
- Overexpression of ERG 11
- Point mutations in ERG11
NOTE: ALL transcription regulation mediated (NOT plasmid mediated)
What does cross-resistance to azoles mean?
If fungi are resistant to even just one type of azole, they are resistant to ALL other azoles
How do drug-drug interactions cause anti-fungal drug toxicity?
EXAMPLE: statins
The liver enzyme CYP3A4 clears statins but when given with azoles, CYP3A4 is responsible for clearing both so it is less efficient => toxic levels of statin in the blood
4 types of human fungal infections?
- Cutaneous infections causing dermatophytosis or “ringworm”
- Mucosal caused by Candida species: candidiasis
- Hospital-acquired, blood-borne infections: Candidiasis
- Acquired from the environment from aerosols causing respiratory infections, then disseminated; Cryptococcosis and Aspergillosos, Histoplasmosis
2 mucosal diseases caused by Candida?
- Oral thrush
2. Vaginitis
What 3 populations are at higher risk of candidiasis?
- HIV/AIDS patients
- Diabetics
- Patients treated with broad spectrum ABs
What Candida species causes oral thrush?
C. albicans and fluconazole resistant non-albicans species
Treatment for candidiasis?
Fluconazole mainly
What is an important statistic to know regarding invasive fungal infections?
As many or more die from invasive fungal infections than drug-resistant TB OR malaria
What % of nocosomial infections are resistant to 1 or more antibiotics?
70%
Most common site of infection for nocosomial infections?
Catheter associated UTI
Ranking of candidiasis causing blood stream infections in the US?
4
Cell wall of candida?
Gram +
What to note about Candida glabrata?
Resistant to many anti-fungals
3 risk factors for developing hospital acquired fungal infections?
- Surgery
- Indwelling devices
- ICU
How to assess the risk of a patient in the hospital ICU? How does it work? Purpose?
APACHE score = acute physiology and chronic health evaluation: patients evaluated during first 24-32 hr after admission to the ICU with 8 classes and a total of 34 variables, each given a score of 0-4 => higher APACHE = greater risk
Purpose: provides initial risk stratification for predicting mortality
What APACHE score indicates a high risk for infections like candidiasis?
> 15
Are blood cultures helpful for detecting septicemia (blood infection) due to candidiasis?
Not really, because only positive 50% of the time
Difference between bacteria and fungi on microscopy? What to note?
Fungal cells are much larger
NOTE: morphology similar to cocci though
3 forms of C. albicans?
- Yeast
- Pseudohyphae
- True hyphae
What Candida species cause blood stream infections?
C. albicans
Form of Candida glabrata in tissues?
Yeast and some filamentation
2 species of Cryptococcus? Which is more common?
- ***Cryptococcus neoformans
2. Cryptococcus gattii
How do Cryptococci grow?
As unicellular yeasts
How are Cryptococci infections acquired?
Environmentally acquired by inhalation
What is the only fungal pathogen with a capsule? What is it? Implication?
Cryptococci (polysaccharide capsule) => basis for lab identification
Most common underlying issue of Cryptococci infections?
HIV/AIDS
Mortality of Cryptococci infections?
Exceeds drug-resistant TB
Staining for Cryptococci?
India ink because cannot penetrate the capsule
How does CSF differ in bacterial and fungal infections?
WBCs in thousands per micro L in bacterial infections
Temperature in fungal infections?
Not as elevated as in bacterial infections
Treatment for Cryptococci infections?
- Inductive: Amphotericin B + fluconazole
2. Maintenance: fluconazole for life once infection has cleared
What disease can Cryptococci infections cause?
Meningitis
What is aspergillosis?
Caused by infection with the pathogen Aspergillus fumigatus
How are Aspergillus fumigatus infections acquired?
Inhalation of air-borne spores
Can humans be carriers of Aspergillus fumigatus?
YUP as the organism can survive in the upper respiratory tract without any symptoms
What does the type of Aspergillosis depend on? Which is most common?
Immune status of the patient:
- Immune dysfunction (neutropenia): acute and subacute invasive infections
- ***Immune hyperactivity: allergic sinusitis, severe asthma with fungal sensitization, ABPA (in cystic fibrosis patients due to a genetic defect)
- Healthy: aspergilloma (in lungs), chronic cavitary, chronic fibrosing, locally invasive
What are 7 characteristics of fungal infections endemic to the US?
- Environmental fungal pathogens: they are acquired by inhalation of spore aerosols resulting in respiratory diseases
- Grow in the environment
- Dimorphic growth: can be seen in both yeast and filamentous fungi
- Cause epidemics: common source or focal epidemics
- Cause disease in otherwise healthy patients
- Protection is associated with T Cell function: hence also occur in HIV/AIDS patients and
disease progresses more quickly if untreated - Treated with azoles
Describe the Histoplasmosis endemic in the US.
Was caused by the Histoplasma capsulatum pathogens with aerosols of spores in the soil being disrupted => spores were released and inhaled => most commonly seen along the Mississippi- Ohio- and Missouri rivers in both major cities and rural areas
NOTE: the epidemic was environment to person (focal or common source) NOT person to person
Describe the Coccidioidomycosis endemic in the US. What was it known as?
Also known as “Valley fever” or “Valley bumps,” this pathogenic fungus is endemic to the Southwest in late summer/early fall
The fungus, Coccidioides immits, is present in the
soil and carried by wind currents. It is pseudofilamentous and has spores. Once it was inhaled symptoms did not appear until 6 months later due to the very long incubation period.
NOTE: the epidemic was environment to person (focal or common source) NOT person to person
What to note about both endemic mycoses? 3
- Epidemics can involve small or large numbers of individuals exposed to the organism
- Disease severity related to inhalation dosage by individuals (asymptomatic to sick)
- Therapy was needed for ~ 40% of infected
Symptoms of Histoplasmosis? What to note?
- Chest pain
- Systemic involvement
- Pericarditis
NOTE: symptoms more severe in males
Treatment for Histoplasmosis?
Amphotericin B
Why was the Coccidioidomycosis endemic called “Valley bumps”
Skin reaction in women indicative of protection
2 global fungal infections?
- Candidiasis
2. Cryptococcosis
