lect. 8
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Questions and Answers

What is the effect of azoles and amphotericin B on membrane homeostasis?

  • Activating stress pathways, leading to increased membrane rigidity
  • Disturbing cellular ergosterol content, leading to membrane destabilization and subsequent lysis of the cell (correct)
  • Increasing cellular ergosterol content, leading to membrane stabilization and cell growth
  • Inhibiting efflux pumps, leading to decreased membrane fluidity
  • What is the role of Hsp90 chaperone in stress signaling?

  • Activation of apoptosis under stressful conditions
  • Involvement in protein folding and stabilizing many proteins involved in signal transduction (correct)
  • Inhibition of protein synthesis under stress conditions
  • Stimulation of efflux pump expression
  • What is the resistance mechanism found in many fungal species due to overexpression of specific efflux pumps?

  • Inhibition of mitochondrial function
  • Excretion of antifungal compounds (correct)
  • Activation of stress pathways
  • Increased cell growth
  • What is the effect of mitochondrial alterations on fluconazole resistance?

    <p>Increased fluconazole resistance due to loss of mitochondrial function</p> Signup and view all the answers

    Antifungal compounds used in clinical therapy only target mechanisms present in fungi and do not affect human cells.

    <p>True</p> Signup and view all the answers

    Invasive fungal infections are often caused by non-pathogenic fungi.

    <p>False</p> Signup and view all the answers

    Successful clinical outcome of invasive fungal infections requires early diagnosis and effective antifungal therapy.

    <p>True</p> Signup and view all the answers

    Overexpression of efflux pumps is the resistance mechanism found in all fungal species including echinocandin or polyene-resistant fungal isolates.

    <p>False</p> Signup and view all the answers

    Mitochondrial alterations have no effect on fluconazole resistance.

    <p>False</p> Signup and view all the answers

    Cellular stress signaling does not provide protection against drug-induced stress conditions.

    <p>False</p> Signup and view all the answers

    Changing the ratio of phospholipid species (PLs) does not impact membrane homeostasis.

    <p>False</p> Signup and view all the answers

    Acquired resistance to antifungal drugs is mainly a result of mutations or gene gain

    <p>True</p> Signup and view all the answers

    Echinocandins are equally effective against all Candida species

    <p>False</p> Signup and view all the answers

    Polyene drugs cause cell death in fungi by binding to ergosterol in the fungal plasma membrane

    <p>True</p> Signup and view all the answers

    ABC or MFS transporters are the primary targets of echinocandins and polyene-resistant fungal isolates.

    <p>False</p> Signup and view all the answers

    Mitochondrial alterations have been reported to facilitate fluconazole resistance in C. glabrata.

    <p>True</p> Signup and view all the answers

    Hsp90 chaperone is not involved in stress signaling and protein stabilization.

    <p>False</p> Signup and view all the answers

    Study Notes

    Antifungal Drug Resistance: Mechanisms and Implications

    • Drug resistance severely limits therapy due to few treatment options
    • Intrinsic resistance occurs naturally without mutation or gene gain
    • Acquired resistance results from evolutionary adaptation to antibiotics
    • Azole resistance is substantial among Candida and Aspergillus species
    • Mechanisms of azole resistance include upregulation of drug transporters and alterations in drug target
    • Efflux pumps and modifications to the sterol biosynthesis pathway are common causes of azole resistance
    • Polyene drugs bind ergosterol in fungal plasma membrane, causing cell death
    • Polyene resistance is caused by loss-of-function mutations in ergosterol biosynthesis gene
    • Echinocandins are effective against most Candida species but less active against Candida parapsilosis
    • Echinocandin resistance is associated with genetic mutations in FKS genes
    • Biofilms protect against antifungal compounds and increase adherence to host surfaces
    • Mechanisms of antifungal resistance include structural target site alterations and metabolic bypass

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