• New approach could overcome fungal resis

    From ScienceDaily@1:317/3 to All on Wed Nov 17 21:30:42 2021
    New approach could overcome fungal resistance to current treatments


    Date:
    November 17, 2021
    Source:
    American Chemical Society
    Summary:
    Current medications aren't particularly effective against fungi. The
    situation is becoming more challenging because these organisms
    are developing resistance to antimicrobial treatments, just as
    bacteria are.

    Now, researchers report that they have identified compounds that
    tackle these infections in a new way -- by interfering with fungal
    enzymes required for fatty acid synthesis -- potentially opening
    the door to better therapies.



    FULL STORY ========================================================================== Current medications aren't particularly effective against fungi. The
    situation is becoming more challenging because these organisms are
    developing resistance to antimicrobial treatments, just as bacteria
    are. Now, researchers report in ACS Infectious Diseases that they have identified compounds that tackle these infections in a new way -- by interfering with fungal enzymes required for fatty acid synthesis -- potentially opening the door to better therapies.


    ========================================================================== Superficial infections by Candida or other types of fungi can cause
    irritating but relatively minor conditions such as oral thrush and
    athlete's foot, but invasive infections can result in debilitating and
    deadly diseases such as cryptococcal meningitis and some hospital-acquired infections. More people are getting these infections because of the
    growing use of invasive surgery, implanted catheters and immunosuppressive therapy. And some patients, such as those with severe COVID-19 or HIV,
    are especially susceptible to fungal infections. In addition, treatments
    can be toxic and often don't work, in part because of increasing
    resistance. Current targets for these compounds include molecules
    necessary for making fungal cell walls. As an alternative, Glen. E.

    Palmer and colleagues began looking for potential therapies that could
    work through a different mechanism and thereby avoid the drawbacks of
    these drugs.

    The researchers zeroed in on fungal fatty acid (FA) synthase and
    desaturase enzymes, which are essential for the growth and virulence of
    human fungal pathogens. It's been difficult to devise a rapid chemical
    assay to find inhibitors for these enzymes, since it's hard to isolate
    the enzymes. So the team instead combined genetic engineering with
    a whole-cell assay to screen thousands of small molecules. Although
    none of the tested compounds blocked FA synthase activity in Candida
    albicans cell cultures, 16 inhibited FA desaturase activity. A core
    acyl hydrazide structure was found to be key to the activity of several
    of these molecules, which were effective even against drug-resistant
    strains of several infectious species of fungi, while showing little to
    no toxicity to mammalian cells. The researchers note that these compounds
    are promising leads for further development as antifungal agents.

    ========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Christian DeJarnette, Chris J. Meyer, Alexander R. Jenner,
    Arielle Butts,
    Tracy Peters, Martin N. Cheramie, Gregory A. Phelps, Nicole A. Vita,
    Victoria C. Loudon-Hossler, Richard E. Lee, Glen E. Palmer.

    Identification of Inhibitors of Fungal Fatty Acid Biosynthesis. ACS
    Infectious Diseases, 2021; DOI: 10.1021/acsinfecdis.1c00404 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2021/11/211117100048.htm

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