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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