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Reversal of Tetracycline Resistance by Cepharanthine, Cinchonidine, Ellagic Acid and Propyl Gallate in a Multi-drug Resistant Escherichia coli |
| Darko Jenic1, Helen Waller2, Helen Collins3, Clett Erridge1 |
1 School of Life Sciences, Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK;
2 Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK;
3 Department of Health Sciences, University of Leicester, University Rd, Leicester LE1 7RH, UK |
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Abstract Bacterial resistance to antibiotics is an increasing threat to global healthcare systems. We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli (NCTC 13400). 200 natural compounds with a history of either safe oral use in man, or as a component of a traditional herb or medicine, were screened. Four compounds; ellagic acid, propyl gallate, cinchonidine and cepharanthine, lowered the minimum inhibitory concentrations (MICs) of tetracycline, chloramphenicol and tobramycin by up to fourfold, and when combined up to eightfold. These compounds had no impact on the MICs of ampicillin, erythromycin or trimethoprim. Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells, the other hit compounds slowed cellular accumulation of this marker, and/or slowed bacterial growth in the absence of antibiotic. Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model, the other hit compounds exhibited no toxicity at concentrations where they are active against E. coli NCTC 13400. The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated, and may offer useful scaffolds for the development of antibiotic-sensitising drugs.
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| Keywords
Antibiotic resistance
Natural products
Phytochemical
Screening
Efflux pump inhibitor
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| Fund:This work was supported by an Erasmus+ Mobility Studentship (ref DK KOBENHA 57) awarded to DJ. The funder was not involved in the interpretation of results or writing of the article. |
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Corresponding Authors:
Clett Erridge
E-mail: clett.erridge@aru.ac.uk
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Issue Date: 04 June 2021
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