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        New approach could overcome

        fungal resistance to current


              urrent medications aren’t
              particularly effective
        Cagainst 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         pathogens. It’s been difficult      note that these compounds
        with severe COVID-19 or HIV, are     to devise a rapid chemical          are promising leads for further
        especially susceptible to fungal     assay to find inhibitors for        development as antifungal agents.
        infections. In addition, treatments   these enzymes, since it’s hard
        can be toxic and often don’t work,   to isolate the enzymes. So the      Story Source:
        in part because of increasing        team instead combined genetic       Materials provided by American
        resistance. Current targets for these   engineering with a whole-cell    Chemical Society. Note: Content
        compounds include molecules          assay to screen thousands of        may be edited for style and length.
        necessary for making fungal cell     small molecules. Although none
        walls. As an alternative, Glen. E.   of the tested compounds blocked     Journal Reference:
        Palmer and colleagues began          FA synthase activity in Candida     1. Christian DeJarnette, Chris
        looking for potential therapies that   albicans cell cultures, 16 inhibited   J. Meyer, Alexander R. Jenner,
        could work through a different       FA desaturase activity. A core      Arielle Butts, Tracy Peters,
        mechanism and thereby avoid the      acyl hydrazide structure was        Martin N. Cheramie, Gregory A.
        drawbacks of these drugs.            found to be key to the activity     Phelps, Nicole A. Vita, Victoria C.
                                             of several of these molecules,      Loudon-Hossler, Richard E. Lee,
        The researchers zeroed in on         which were effective even against   Glen E. Palmer. Identification of
        fungal fatty acid (FA) synthase      drug-resistant strains of several   Inhibitors of Fungal Fatty Acid
        and desaturase enzymes, which        infectious species of fungi, while   Biosynthesis. ACS Infectious
        are essential for the growth         showing little to no toxicity to    Diseases, 2021; DOI: 10.1021/
        and virulence of human fungal        mammalian cells. The researchers    acsinfecdis.1c00404

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