Yadav, S and Singh, AK and Agrahari, AK and Pandey, AK and Gupta, MK and Chakravortty, D and Tiwari, VK and Prakash, P (2021) Galactose-clicked curcumin-mediated reversal of meropenem resistance among klebsiella pneumoniae by targeting its carbapenemases and the AcrAB-TolC efflux system. In: Antibiotics, 10 (4).
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Abstract
In over eighty years, despite successive antibiotics discoveries, the rapid advent of multidrug resistance among bacterial pathogens has jolted our misapprehension of success over them. Resistance is spreading faster than the discovery of new antibiotics/antimicrobials. Therefore, the search for better antimicrobials/additives becomes prudent. A water-soluble curcumin derivative (Curaq) was synthesised, employing a Cu (I) catalysed 1, 3-cyclo addition reaction; it has been evaluated as a potential treatment for multidrug-resistant isolates and as an antibiotic adjuvant for meropenem against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. We also investigated its solubility and effect over carbapenemase activity. Additionally, we investigated its impact on the AcrAB-TolC system. We found that Curaq inhibited bacterial growth at a minimal concentration of 16 ug/mL; at a 32 ug/mL concentration, it killed bacterial growth completely. Only nine (9.4) Klebsiella isolates were sensitive to meropenem; however, after synergising with Curaq (8 ug/mL), 85 (88.54) hvKP isolates became sensitive to the drug. The Curaq also inhibited the AcrAB-TolC efflux system at 1 ug/mL concentration by disrupting the membrane potential and causing depolarisation. The kinetic parameters obtained also indicated its promise as a carbapenemase inhibitor. These results suggest that Curaq can be an excellent drug candidate as a broad-spectrum antibacterial and anti-efflux agent. © 2021 by the authors.
| Item Type: | Journal Article |
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| Publication: | Antibiotics |
| Publisher: | MDPI AG |
| Additional Information: | The copyright for this article belongs to Authors |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 11 Aug 2021 09:05 |
| Last Modified: | 11 Aug 2021 09:05 |
| URI: | http://eprints.iisc.ac.in/id/eprint/69105 |
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