22. Mycology Flashcards
most fungal pathogens are acquired from_____, EXCEPTION: _____.
environment or part of normal microbiota
EXCEPTION: candida.
Important factors for immunity against fungal infections and what happens when they’re compromised:
- Innate – neutrophils (neutropenia, in cancer and immunosuppressed transplant pts invasive candidiasis infections)
- Tcells – CD4 and CD8 (in AIDS pts mucosal candiasis, cryptococcosis and histoplasmosis infections)
- B cells – Antibody – rare, cryptococcosis.
Antifungal drugs and their targets: (3)
- cell wall inhibitors - echinocandins
- disrupt membrane sterols
- Inhibit membrane sterols – Azoles and polyenes (targets ergosterol, but also binds to cholesterol and causes problem!)
Some problems with treating fungal pathogens:
1) Fungi are euk just like us, so there is a problem of toxicity. ex: some antifungal drugs target ergosterol (fungal plasma membrane), which is similar to cholesterol in human plasma membrane and causes toxicity.
2) multiple growth forms: unicellular, filamentous or in between (yeast, hyphae/mycelium vs. pseudohyphae).
3) most are acquired from environment or are part of microbiota.
4)
Why are fungi that form spores particularly problematic?
1) spores are aerosolized infectious particles, that can cause disease via inhalation IMPORTANT
2) In culture and in host, spores can germinate and start to form tubes that grow into tissues and cause disease (hyphae structures).
immunity to mucosal vs. invasive candidiasis
Invasive candidiasis – innate immunity more important, see infec in pts with neutropenia (low neutrophil count), in chemotherapy and immunosuppressed transplant pts.
Mucosal candidiasis – T-cells, in AIDS pts (bc low CD4/8 cells)
Problems with antifungals:
- lack of variety of drugs (only 3 kinds)
- increasing resistance (candida)– especially with azoles, echinocandins.
- Echinocandins are not broad spectrum
- Toxicity and drug-drug interactions (azoles).
Mechanisms for resistance to Azoles:
- overexpression and increase in number of efflux pumps that pump out the drug (CDR1, CDR2, MDR)
- overexpression or mutation of the target of the drug (azoles target ERG11, enzyme involved in synthesis of ergosterol). Not enough drugs to have any effect/drug cant bind anymore (mutation).
- cross resistance to azoles (resistant to one azole, but no other azole will work).
How is resistance to azoles developed?
- NOT via plasmids
- via changes in transcriptional regulation (or mutation)
What drug interacts with Azoles?
Statins (high BP) – degraded by CYP3A4 (liver enzyme)
Statins+Azole = toxicity (azole inhibits CYP3A4, which can’t degrade statins anymore).
Mucosal infections caused by candida:
- oral thrush and vaginitis
- in AIDS pts, diabetics, and women treated with broad-spectrum antibiotics.
4 categories of fungal infections:
1) cutaneous infections: ringworms
2) Mucosal: caused by candida (candidiasis), common in AIDS pts
3) Hospital acquired, blood-borne infections: candidiasis
4) acquired from environment (aerosol) respiratory, then decimated.
Fungal growth forms
- unicellular
- filamentous and produce spores
- both unicellular and filamentous/spores
Death from invasive fungal infections exceed ___, equal in frequency to _____
exceeds maleria, equals drug-resistant TB
Candidiasis is the ___th cause of hospital acquired Blood stream infections (BSI).
3-4th
