Econazole as adjuvant to conventional antibiotics is able to eradicate starvation-induced tolerant bacteria by causing proton motive force dissipation.

Abstract

OBJECTIVES:

Bacterial antibiotic tolerance is responsible for the recalcitrance of chronic infections. This study aims to investigate a potential drug that can effectively kill antibiotic-tolerant bacteria and evaluate the ability of this drug on the eradication of tolerant cells both in vitro and in vivo.

METHODS:

The in vitro effect of econazole on eradicating starvation-induced tolerant bacterial populations was studied by testing the amount of survival bacteria in the presence of econazole combining conventional antibiotics. Proton motive force (PMF) was determined after econazole treatment by DiOC2(3). Finally, mouse infection models were used to detect the ability of econazole on killing the tolerant populations in vivo.

RESULTS:

Econazole eradicated starvation-induced tolerant cells of various bacterial species within 24 or 96 h when used in combination with conventional antibiotics. Moreover, mouse survival rate drastically increased along with the decrease of in vivo bacterial count after treatment of infected mice with the econazole and ceftazidime combination for 72 h. PMF was found to have dissipated almost completely in econazole-treated cells.

CONCLUSIONS:

Econazole could act in combination with conventional antibiotics to effectively eradicate bacterial tolerant cells. The combined use of econazole and ceftazidime was shown to be effective for eradicating tolerant cells in a mouse infection model. The ability of econazole to eradicate tolerant cells was due to its ability to cause dissipation of bacterial transmembrane PMF. Econazole-mediated PMF disruption is a feasible strategy for the treatment of chronic and recurrent bacterial infections.

• Authors: Miaomiao Wang, Edward Wai Chi Chan, Chen Xu, Kaichao Chen, Chen Yang, Sheng Chen
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 77 Issue 2 Pg. 425-432 (02 02 2022) ISSN: 1460-2091 [Electronic] England
• PMID: 34747463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Adjuvants, Pharmaceutic
• Anti-Bacterial Agents
• Econazole

Topics

• Adjuvants, Pharmaceutic
• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacteria
• Econazole (pharmacology)
• Mice
• Proton-Motive Force