LECTURE 14 (Mycology) Flashcards
What are the two types of Fungi?
Yeasts and Molds
- Yeasts = grow as single cells that reproduce by asexual budding
- Molds = grow as long filaments (HYPHAE) + form a mat (MYCELIUM)
Describe Hyphae
- Some hyphae form transverse walls (SEPTATE HYPHAE), whereas others don’t (NON-SEPTATE HYPHAE)
- NON-SEPTATE HYPHAE are multinucleated (Coenocytic)
- SEPTATE HYPHAE contain pores and septums, non-septate hyphae do not
- Growth of hyphae occurs by extension of tip of hyphae (not by cell division)
What does the term “thermally dimorphic” mean?
Form different structures at different temperatures
EXAMPLE: some fungi exist as moles in the environment at ambient temperature and as yeasts in human tissues at body temperature
Describe Fungi
- Most are obligate aerobes/facultative aerobes
- Require a preformed organic source of carbon
- Natural habitat is the environment (apart from “Candida albicans” which is part of the normal human flora)
Describe the two fungal cell structures that are important clinically
- The fungal cell wall is made of CHITIN
[bacterial cell wall is made of peptidoglycan so antibiotics (penicillin, cephalosporins, antibiotics) are not effective against fungi] - Fungal cell membrane contains ERGOSTEROL
[human cell membrane contain cholesterol so amphotericin B and azole drugs (fluconazole and ketoconazole) target fungi]
What are the two types of fungi?
- True pathogenic fungi
- Opportunistic fungi
What are the steps of pathogenesis of fungi?
1) ADHERENCE
[colonisation of mucosal surfaces of the GI and female genital tracts]
2) INVASION
[passing an initial surface barrier (skin, mucous membrane or respiratory epithelium) - may involve enzymes]
3) INJURY
[due to inflammatory and immunologic responses + NO EXOTOXINS!!!]
Describe the pathogenesis of Fungal infections
- Formation of granulomas
[cell-mediated immune response is involved in granuloma formation] - Acute suppuration
[characterised by presence of neutrophils] - NO ENDOTOXIN OR EXOTOXIN!!!!
Describe the testing for fungal infections
- Activation of the cell-mediated immune system results in a DELAYED HYPERSENSITIVITY SKIN TEST response to fungal antigens injected INTRADERMALLY
- POSITIVE SKIN TEST indicates exposure to fungal antigen
[does not imply current infection] - Skin testing with “CANDIDA” antigens used to determine normal cell-mediated immunity
[since “Candida” in part of normal flora]
What are the different Toxins and Allergies from fungi?
- Ingestion of AMANITA mushrooms causes LIVER NECROSIS due to presence of two fungal toxins, “AMANITIN” and “PHALLOIDIN” -> Amanitin inhibits the RNA polymerase that synthesises cellular mRNA
- Ingestion of peanuts and grains contaminated with ASPERGILLUS FLAVUS causes LIVER CANCER due to presence of AFLATOXIN -> AFLATOXIN EPOXIDE induces a mutation in the p53 gene resulting in loss of p53 tumour suppressor gene
- Inhalation of spores of ASPERGILLUS FUMIGATUS can cause ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS -> IgE mediated immediate hypersensitivity response
What are the different types of fungal infections in humans?
- Superficial fungal infections
[OUTERMOST LAYERS of stratum corneum of skin or cuticle of hair shaft + usually cosmetic problems + rarely an immune response] - Dermatophyte infections
[affect hair, nails and skin] - Subcutaneous mycoses
[abundant in environment + low degree of infectivity + gain access to subcutaneous tissues through traumatic implantation] - Systemic mycoses
[primary site of infection is respiratory tract]
What are the only 6 agents that cause systemic mycoses?
- Histoplasma capsulatum
- Blastomyces dermatitidis
- Paracoccidiodes Brasiliensis
- Coccidiodes Immitis
- Penicillium marneffei
Describe the immune response against fungal infections
- Mucous membranes of the nasopharynx -> trap inhaled fungal spores and alveolar macrophages
- Most fungi readily killed by neutrophils
- Fungi that escape neutrophils grow slowly in macrophages + growth restricted when macrophages activated by cytokines
- Progressive fungal diseases occur in immune-compromised people
What are the different lab diagnosis for Fungal infections?
- Direct examination
[KOH, gram stain, skin biopsy] - Culture
[Sabouraud’s agar optimal for fungi] - Biochemical tests
[yeasts identified by biochemical tests (e.g urease production) + ability to form pseudohyphae] - DNA probes
- Antigen and antibody detection
What are the different Antifungal drugs?
- SERTACONAZOLE -> binds non-sterol lipids + alters cell membrane integrity
- POLYENES (amphotericin B + nystatin) -> Binds ergosterol + disrupts membrane integrity
- ECHINOCANDINS (anidulafungin, caspofungin and micafungin) -> Inhibit the glugan biosynthesis pathway
- AZOLES (flucanozole, miconazole, and sertaconazole) -> Inhibit the ergosterol biosynthesis pathway
- FLUROCYTOSINE -> Inhibit nucleic acid synthesis
ADDITIONAL INFO: most fungal infections are self-limiting and require no chemotherapy -> treatment is important for dissemination in immunocompromised people