Fungi intro Flashcards
Explain the classification and structure of fungi.
3 main groups:
- Basidiomycetes
- Ascomycetes Saccharomyces
- Zygomycetes
(each has a sexual and asexual spore)
A chemo-organotrophic eukaryote that lacks chlorophyll and forms spores. Its cell wall contains polysaccharides, often chitin or glucan, and it absorbs nutrients. Its membrane contains ergosterol as the major sterol. Classification is principally based on morphology (shape/form).
Describe the clinically important systemic and dermatophytic fungal infections.
Systemic Fungal Infections
Candidiasis:
Causative Agent: Candida albicans and other Candida species.
Clinical Manifestations: Ranges from superficial infections (e.g., oral thrush, vaginal yeast infections) to systemic infections, which can affect the bloodstream (candidemia) and internal organs.
Risk Factors: Immunocompromised individuals, diabetes, prolonged antibiotic use, and indwelling medical devices.
Aspergillosis:
Causative Agent: Aspergillus species, particularly A. fumigatus.
Clinical Manifestations: Can present as allergic reactions (allergic bronchopulmonary aspergillosis), localized lung infections (aspergilloma), or invasive pulmonary aspergillosis in immunocompromised patients.
Risk Factors: Neutropenia, prolonged corticosteroid use, and lung diseases.
Cryptococcosis:
Causative Agent: Cryptococcus neoformans and Cryptococcus gattii.
Clinical Manifestations: Often causes meningitis, particularly in immunocompromised patients (e.g., those with HIV/AIDS). It can also affect the lungs and skin.
Risk Factors: Immunocompromised states, particularly in individuals with CD4 counts below 200 cells/mm³.
Histoplasmosis:
Causative Agent: Histoplasma capsulatum.
Clinical Manifestations: Primarily affects the lungs, causing pneumonia-like symptoms. It can become disseminated in immunocompromised individuals.
Risk Factors: Exposure to bird or bat droppings, particularly in endemic areas (e.g., Ohio and Mississippi River valleys).
Coccidioidomycosis (Valley Fever):
Causative Agent: Coccidioides immitis and C. posadasii.
Clinical Manifestations: Can cause respiratory symptoms, and in some cases, disseminated disease affecting the skin, bones, and meninges.
Risk Factors: Living in or visiting endemic regions (e.g., southwestern United States).
Dermatophytic Fungal Infections
Tinea (Ringworm):
Causative Agents: Dermatophyte fungi, including Trichophyton, Microsporum, and Epidermophyton species.
Clinical Manifestations:
Tinea capitis: Scalp infection, common in children.
Tinea corporis: Body ringworm, characterized by circular, itchy patches.
Tinea pedis: Athlete’s foot, affecting the feet and often between the toes.
Tinea cruris: Jock itch, affecting the groin area.
Tinea unguium (Onychomycosis): Nail infections, often leading to thickened, discolored nails.
Risk Factors: Warm, humid environments, close contact with infected individuals or animals, and compromised skin barriers.
Describe the properties of fungi
Eukaryotic Cells: Fungi are made up of eukaryotic cells, which contain a defined nucleus and organelles.
Cell Wall Composition: Their cell walls are primarily made of chitin, a strong polysaccharide, unlike plants, which have cellulose in their walls.
Heterotrophic Nutrition: Fungi are heterotrophs, meaning they obtain nutrients by absorbing organic matter from their environment. They do this through external digestion, releasing enzymes to break down complex substances into simpler compounds.
Reproductive Strategies: Fungi can reproduce both sexually and asexually. Asexual reproduction often occurs through spores, budding, or fragmentation, while sexual reproduction involves the fusion of specialized reproductive structures.
Mycelium Structure: Fungi grow as a network of filaments called hyphae, which collectively form a mycelium. This structure increases their surface area for nutrient absorption.
Symbiotic Relationships: Many fungi form symbiotic relationships with other organisms, such as mycorrhizal fungi with plants (enhancing nutrient uptake) and lichens (combinations of fungi and algae or cyanobacteria).
Diverse Habitats: Fungi can thrive in a variety of environments, from soil and decaying matter to extreme conditions, such as high salinity or low temperatures.
Role in Ecosystems: They play crucial roles in ecosystems as decomposers, breaking down organic matter and recycling nutrients back into the environment.
Medical and Industrial Importance: Fungi are essential in medicine (e.g., antibiotics like penicillin), food production (e.g., yeast in baking and brewing), and biotechnology.
Variety: There are over 1.5 million estimated fungal species, ranging from yeasts and molds to large fruiting bodies like mushrooms.
Describe the host factors that contribute to the pathogenicity of fungal infections
Immune System Status: A weakened immune system, whether due to conditions like HIV/AIDS, cancer, or immunosuppressive therapies, makes individuals more susceptible to fungal infections. Fungi can exploit gaps in immune defenses.
Age: Infants and elderly individuals often have less robust immune responses, increasing their vulnerability to infections.
Underlying Health Conditions: Chronic illnesses such as diabetes, liver disease, or respiratory disorders can predispose individuals to fungal infections by altering normal immune responses.
Skin Integrity: Compromised skin barriers, such as cuts, wounds, or conditions like eczema, can provide entry points for pathogenic fungi.
Microbiome Composition: The presence of beneficial microbes in the body can help prevent fungal overgrowth. Disruption of the microbiome, often due to antibiotics or other factors, can lead to fungal infections, such as candidiasis.
Nutritional Status: Malnutrition or specific nutrient deficiencies can impair immune function and increase susceptibility to infections.
Hormonal Factors: Hormonal changes, such as those during pregnancy or with the use of hormonal therapies, can affect the immune response and increase vulnerability to certain fungi.
Describe the diagnostic methods for detecting fungi
> Direct detection
- Histopathology
- High-res CT scans
- Direct smear
> Other options
- Detection of circulating fungal antigens
- Detection of circulating antibodies to fungi
- PCR for fungal DNA
- Culture of fungus from normally sterile site
Describe the mechanisms of action of anti-fungal drugs, their route of administration and issues associated with anti-fungal agents
Mechanisms of Action
Inhibition of Cell Wall Synthesis:
Drugs: Echinocandins (e.g., caspofungin, micafungin).
Mechanism: These drugs inhibit the synthesis of beta-glucans, key components of the fungal cell wall, leading to cell lysis and death.
Inhibition of Ergosterol Synthesis:
Drugs: Azoles (e.g., fluconazole, itraconazole) and allylamines (e.g., terbinafine).
Mechanism: Azoles inhibit the enzyme lanosterol demethylase, disrupting the conversion of lanosterol to ergosterol, a crucial component of the fungal cell membrane. This leads to membrane destabilization. Allylamines inhibit squalene epoxidase, affecting ergosterol production indirectly.
Disruption of Cell Membrane Integrity:
Drugs: Polyenes (e.g., amphotericin B, nystatin).
Mechanism: Polyenes bind to ergosterol in the fungal cell membrane, forming pores that lead to leakage of essential intracellular components, resulting in cell death.
Inhibition of Nucleic Acid Synthesis:
Drugs: Flucytosine.
Mechanism: Flucytosine is converted to 5-fluorouracil in fungal cells, interfering with RNA and DNA synthesis, which inhibits fungal growth.
Routes of Administration
Oral:
Common for azoles (e.g., fluconazole, itraconazole) and allylamines (e.g., terbinafine).
Used for mild to moderate infections and for maintenance therapy.
Intravenous (IV):
Often used for severe infections or when oral administration is not feasible.
Amphotericin B and echinocandins are typically administered via IV.
Topical:
Used for superficial infections, particularly dermatophytoses and candidiasis.
Includes topical azoles, polyenes, and allylamines.
Intravaginal:
Common for treating vaginal yeast infections, using topical azoles or creams.
Issues Associated with Antifungal Agents
Resistance:
Fungal species can develop resistance, particularly with azoles and echinocandins, making some infections harder to treat.
Side Effects:
Common side effects include nausea, vomiting, and liver toxicity (especially with azoles).
Amphotericin B can cause renal toxicity and infusion-related reactions.
Drug Interactions:
Antifungals can interact with other medications, particularly azoles, which can inhibit cytochrome P450 enzymes, affecting the metabolism of various drugs.
Cost and Availability:
Some antifungal agents, especially new or intravenous formulations, can be expensive and may not be widely available in all healthcare settings.
Therapeutic Monitoring:
Certain antifungal drugs, like amphotericin B and azoles, require therapeutic drug monitoring to avoid toxicity and ensure efficacy.
Adverse Reactions:
Long-term use of antifungals can lead to adverse effects, including organ toxicity and electrolyte imbalances (especially with amphotericin B).
