Microbiology: Fungi Flashcards
Difference btwn fungi and bacteria
- Fungi are eukaryotic, bacteria are prokaryotic
- Also have cell wall, but it is made up of complex polysaccharides (chitin, B-glucan)
- Fungal cell membranes are composed of ergosterol
- Fungi can be dimorphic (only primary fungi), often depending on temperature (thermodimorphic)
- Switch from mold form (@ 25 C: grow via hyphae, multicellular filamentous form w/ apical extension) to yeast form (@ 37 C: grow via budding or fission to make round unicellular colonies)
- Aspergillus is mold only fungi, and candida is yeast only fungi
Reproduction of fungi
- Can reproduce sexually or asexually
- Asexual spores can be sporangiospores, which are contained in the sporangium, or conidospores, which are borne naked on specialized structures called conidia
- Most medically important fungi reproduce asexually
- Once spores find suitable habitat they germinate into germ tube (initial hypha)
- Germ tube grows into larger hypha (vegetative), and eventually sprouts stalks (aerial hypha) to bear conidia and conidiospores
- Hypha are either septate (divided by partitions in cell wall) or non-septate (hollow and multinucleate)
Types of conidiospores
- Spores are always formed from fruiting (aerial) hypha
- Arthrospores are spores that are formed by fragmentation (every other cell dies)
- Blastospores: very small round cells in clusters, formed by budding
- Chlamydospores: larger round cells w/ thicker walls (formed in unfavorable conditions)
Classification of fungi
- Formal taxonomy
- By reproductive cycle (sexual/asexual spores)
- Degree of tissue involvement
- By host response (primary or opportunistic)
Classification by tissue involvement
-Superficial infections: growth restricted to stratum corneum of skin
-Cutaneous fungal infections (dermatophytes): keratinophilic and more invasive than superficial mycoses, but still limited to keratinized tissue
-Mucocutaneous infections: mucous membranes
Subcutaneous infections: subcutaneous tissue due to trauma
-Systemic infections (primary fungi): inhalation or tissue trauma, mostly affects lung or skin, subsequent dissemination is possible
-Systemic infections usually caused by dimorphic (primary) pathogens that are endemic to regions
Classification by host response (primary vs. opportunistic)
- Opportunistic: candida (endogenous flora), aspergilla and cryptococcosis (exogenous)
- Primary: Blastomycosis, histoplasmosis, coccidiomycosis (and paracoccidiodomycosis), penecilliosis (all exogenous)
Immune response to fungi
- Cell-mediated immunity more important than humoral immunity
- PMNs, macrophages, T cells are all involved in eliminating the infection (phagocytes recognize PAMPs on fungi; pathogen-associated molecular patterns)
- Of the T cells mostly Th1 is involved
- Abs do have role (but not neutralizing except for toxins): prevention of adherence, opsonization, neutralization of toxins
Immunocompromised hosts
- Most patients of fungal infections are IC’d (often infected w/ opportunistic fungi)
- Includes: patients w/ long antibio Rx, those on immunosuppressive drugs (transplants, autoimmune), radiation/chemo therapy, diabetes (endocrine disorders), AIDS (congenital or acquired immunodeficiencies), malnutrition, low birthweight neonates
- Also: AGED
Ways to Dx fungal infections
- Direct microscopic examination from biopsy (opportunistic can be hard to interpret)
- Culturing and determination through morphological and biochemical criteria (may require weeks b/c primary fungi grow slowly)
- Serology: detect Ab’s in serum (cannot tell if positive test means current or prior infection), skin test (DTH) to measure exposure to fungal Ags (testing cell-mediated immunity)
- Can also detect disseminated Ags in blood, or via DNA probes
Problems w/ fungal testing
- IC’d patients may lack Ab response
- Some opportunistic fungi do not produce Ab response
- DTH response may not occur due to anergic T cells (in IC’d patients)
- Positive DTH test does not distinguish which species (can cross react)
Targets of anti fungal drugs
- Polyenes: target ergosterol on cell membrane (amphotericin B)
- Azoles: interfere w/ ergosterol synthesis (interrupt cell and mitochondrial membrane synthesis)
- Echinocandins: inhibit B-glucan synthesis in cell wall
- Nucleoside analogs: inhibit DNA/RNA synthesis (5-fluorocytosine)
- Grisefulvin: binds to microtubule associated proteins and prevents spindle formation at metaphase (targets keratin, for cutaneous infections)
Coccidiodes Immitis
- A primary fungi that is endemic (to southwest US) and shows thermodimorphism (can infect immune competent host), found in soil
- Forms infectious arthrospores (infects via inhalation)
- Arthrospores swell and develop into spherules filled w/ endospores. Each endospore develops into new spherule
- Arthrospores have antiphagocytic activity, spherules are too large to phagocytose
- Elicits both PMN and CMI (cell-mediated immunity) response (mostly Th1)
Coccidiodes pathogenesis
- Causes coccidiodomycosis
- Inhalation of athrospores causes pulmonary infection (most are asymptomatic)
- 40% have mild-severe symptoms (usually IC’d)
- 5% lead to dissemination (to skin, soft tissue abscesses, bone and joints, meningitis)
- Dx: flu-like symptoms, microscopy of spherules, culture (25C and 37C for both forms), serology (blood Abs, CSF Abs, DTH test)
- Rx: Amphotericin B, itraconazol, fluconazole
Candida Albicans
- Opportunistic fungi of normal flora, often infects patients undergoing antibio therapy, neutropenic, and also AIDS/HIV patients
- Produces pseudohypha (NOT MOLDS), in filamentous form it has better survival against host defenses (phenotype switching)
- Usually lives in yeast form, replicates via budding
- Normally lives in URT, GIT, FGT (female genital tract)
Candida pathogenesis
- Causes candidosis
- Non-systemic infections: mucocutaneous (ileum, esophagus, vaginitis, thrush), cutaneous (dermatitis, keratinitis)
- Systemic: UTI, ednocarditis, meningitis, sepsis
- Dx: microscopy (budding yeast and/or pseudohypha), culture (germ tube test, specimens from blood, sputum, urine), sugar assimilation panel
- Rx: Amphotericin B, fluconazole, caspofungin, 5-flucytosine