Pathogenic Fungi Flashcards
Give some background info on fungi.
- eukaryotes
- incapable of producing food (heterotrophs)
- have rigid cell walls containing polysaccharides (chitin or cellulose)
- cell membrane contains ergosterol as the major sterol
- historically, classification was principally based on morphology, but DNA sequence data are now used to revise fungal taxonomy
informally, major types are: moulds, yeasts, or mushrooms
What are hyphae?
hypha (singular)
- a chain of fungal cells, the basic unit of a fungus
mycelium
- the whole mass of hyphae, branches and associated structures
yeasts are mainly unicellular but some species can form hyphae
How is biofilm formation associated with mortality in c albicans formation?
dispersion of spore can result in these entering the bloodstream, where they can infect multiple organs in the body
What are the different forms of fungi good at doing?
hyphae from better at penetrating surfaces
yeast from is better for circulating in the blood
Why is there not that many antifungal drugs?
- fungi are closely related to humans
- drugs that kill fungi may also cause a lot of damage to human cells
- only recenty seen as a major issue
- can become resistant quickly so not seen as worth it monetarily
What are the different types of fungal infections?
superficial
involve keratinised tissue of nail, hair or skin
subcutaneous
involve primarily subcutaneous tissues, lymphatic vessels and contiguous tissues, usually acquired by trauma
systemic
may involve any organ system, range in severity from subclinical to progressive debilitating disease
Candida spp and Aspergillus spp are becomingly increasingly responsible for fatal diseases. In what conditions are they prevelant?
Candida spp
- infect organs of patients w various immune dysfunction
- eg after abdominal surgery, burns etc (cases often in ICU)
–> can use lactate as substrate, used in saline
Aspergillus spp
- infect organs of patients undergoing treatment
- eg chemotherapy, stem cell transplantation
What are dermatophytes?
fungi that can degrade keratin as a nutrient source
spread by direct contact from other people, animals, and soil, as well as indirectly from fomites
eg Epidermophyton, Microsporum, and Trichopyton spp
Give some information on Candida spp.
- part of gut flora but can affect immune function
- yeasts
- cause of candidiasis
- C. albicans can form hyphae and psuedohyphae (polymorphism)
- C. albicans can switch reversibly between different growth forms and morphologies (integral to commensalism and pathogenesis)
yeast cells are well suited to dissemination, and hyphal cells to tissue invasion
Candida. auris: resistant to all antifungal drugs, current killer in hospitals
Give some info on Aspergillus spp.
- cause of aspergillosis
- moulds
- can penetrate walls of blood vessels, (angio-invasive) but only causes issues in immunocompromised hosts
- ubiquitous in the environment , infections occurs by inhalation of conidia (asexual spores)
- can form a fungus ball in the lung, a clump that does not spread
eg A. fumigatus, A. flavus
Give some info on Cryptococcus spp.
- cause of cryptococcosis which affects the lungs or CNS, among others
eg C. neoformans, C. gattii
What are some diagnostic methods for fungal pathogens?
- direct detection (histopathology, CT scans)
- culture of fungus from normally sterile site
- detection of circulating antigens
- detection of circulating antibodies
- PCR for fungal DNA
- whole genome sequencing
- mass spec
What are the modes of action of different classes of antifungal agents (1)? polyenes, azoles, allylamines
polyenes
–> bind to ergosterol in fungal cell membranes. cause fatal leakage of ions
azoles
–> targets lanosterol-a-demethylase in the ergosterol biosynthesis pathway
allylamines
–> a new class of ergosterol biosynthetic inhibitors
What are the modes of action of different classes of antifungal agents (2)? Pyramindine analogue, griseofluvin, echinocandins
Pyrimidine analogue eg flucytosine
–> interacts w RNA biosynthesis and disturbs the making of certain proteins
–> inhibits fungal DNA synthesis
–> toxic to humans
griseofluvin
–> binds to tubulin, interfering w microtubule function, inhibiting mitosis
–> toxic to humans
echinocandins
–> target Fks1p subunit of 1,3-beta-d-glucan synthase (GS), an enzyme involved in synthesis of b-glucan in cell walls of some fungi
PRR recognise PAMPs on fungal cell wall
duh
