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SPECIALITY

New approach could overcome

fungal resistance to current

treatments

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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