Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection.
OBJECTIVE
There is a need for novel treatments for Clostridium difficile infection(CDI). Antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against Cl. difficile. We explored their anti-difficile properties.


RESULTS
Anti-difficile activities were determined for several naturally occurring flavonoids, olympicin A and synthetic 4-chromanone and chalcone analogues. With the exception of olympicin A, most naturally occurring phytochemicals tested were poorly active. Diversified synthetic flavonoids resembling olympicin A retained anti-difficile activity, suggesting olympicin A could act as a pharmacophore to obtain novel agents. They also demonstrated concentration-dependent killing of logarithmic and stationary phase cultures and reduced sporulation and toxin production. Olympicin A and some synthetic flavonoids dissipated the bacterial transmembrane potential. Interestingly, mutants could only be selected with the analogue 207 at a frequency of 10(-9).


CONCLUSIONS
Based on the potent anti-difficile properties of olympicin A and modified flavonoids, further exploration of this class of phytochemicals is warranted.


CONCLUSIONS
Clostridium difficile infection is a major problem in developed countries. These studies point to there being an avenue for optimizing plant-derived flavonoids, and related antibacterial phytochemicals, as nature-inspired approaches to treat CDI.
X
X
Wu
M Z
MZ
Alam
L
L
Feng
L S
LS
Tsutsumi
D
D
Sun
J G
JG
Hurdle
D000900:Anti-Bacterial Agents / Q000737:chemistry; D001427:Bacterial Toxins; D016360:Clostridioides difficile; D003015:Clostridium Infections; D005419:Flavonoids; D064209:Phytochemicals
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005419:Flavonoids; D064209:Phytochemicals