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

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 DiOC(2)(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.

Automated summary

The study demonstrates that econazole in combination with conventional antibiotics can effectively kill antibiotic-tolerant bacteria by causing the dissipation of bacterial transmembrane proton motive force (PMF). The use of econazole and ceftazidime combination showed promising results in eradicating tolerant cells in a mouse infection model.