Zhang, F;
Zhai, T;
Haider, S;
Liu, Y;
Huang, ZJ;
(2020)
Synergistic Effect of Chlorogenic Acid and Caffeic Acid with Fosfomycin on Growth Inhibition of a Resistant Listeria monocytogenes Strain.
ACS Omega
, 5
(13)
pp. 7537-7544.
10.1021/acsomega.0c00352.
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Abstract
Listeria monocytogenes, a human foodborne pathogen that causes listeriosis with high-rate mortality, has been reported to be resistant to commonly used antibiotics. New antibiotics or cocktails of existing antibiotics with synergistic compounds are in high demand for treating this multi-drug-resistant pathogen. Fosfomycin is one of the novel and promising therapeutic antibiotics for the treatment of listeriosis. However, some L. monocytogenes strains with the FosX gene were recently reported to survive from the fosfomycin treatment. This work aims to identify FosX inhibitors that can revive fosfomycin in treating resistant L. monocytogenes. Since structures and activities of the FosX protein in L. monocytogenes have been well studied, we used an integrated computational and experimental approach to identify FosX inhibitors that show synergistic effect with fosfomycin in treating resistant L. monocytogenes. Specifically, automated ligand docking was implemented to perform virtual screening of the Indofine natural-product database and FDA-approved drugs to identify potential inhibitors. An in vitro bacterial growth inhibition test was then utilized to verify the effectiveness of identified compounds combined with fosfomycin in inhibiting the resistant L. monocytogenes strains. Two phenolic acids, i.e., caffeic acid and chlorogenic acid, were predicted as high-affinity FosX inhibitors from the ligand-docking platform. Experiments with these compounds indicated that the cocktail of either caffeic acid (1.5 mg/mL) or chlorogenic acid (3 mg/mL) with fosfomycin (50 mg/L) was able to significantly inhibit the growth of the pathogen. The finding of this work implies that the combination of fosfomycin with either caffeic acid or chlorogenic acid is of potential to be used in the clinical treatment of Listeria infections.
| Type: | Article |
|---|---|
| Title: | Synergistic Effect of Chlorogenic Acid and Caffeic Acid with Fosfomycin on Growth Inhibition of a Resistant Listeria monocytogenes Strain |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acsomega.0c00352 |
| Publisher version: | https://doi.org/10.1021/acsomega.0c00352 |
| Language: | English |
| Additional information: | This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html), which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
| Keywords: | Organic acids, Chlorogenic acid, Antimicrobial agents, Toxicological synergy, Inhibitors |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10094612 |
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