Zoaiter M., Zeaiter Z., Mediannikov Oleg, Sokhna Cheikh, Fournier P. E. (2023). Carbonyl cyanide 3-chloro phenyl hydrazone (CCCP) restores the colistin sensitivity in Brucella intermedia. International Journal of Molecular Sciences, 24 (3), 2106 [14 p.].
Titre du document
Carbonyl cyanide 3-chloro phenyl hydrazone (CCCP) restores the colistin sensitivity in Brucella intermedia
Zoaiter M., Zeaiter Z., Mediannikov Oleg, Sokhna Cheikh, Fournier P. E.
Source
International Journal of Molecular Sciences, 2023,
24 (3), 2106 [14 p.]
Brucella intermedia (formerly Ochrobactrum intermedium), a non-fermentative bacterium, has been isolated from animals and human clinical specimens. It is naturally resistant to polymyxins, including colistin (CO), and may cause opportunistic infections in humans. We isolated six Brucella intermedia strains from Senegalese monkey stool. In order to determine whether an efflux pump mechanism was involved in CO resistance in B. intermedia, we evaluated the effects of verapamil (VRP), reserpine (RSP), phe-arg beta-naphthylamide dihydrochloride (PA beta N) and carbonyl cyanide 3-chloro phenyl hydrazone (CCCP), four efflux pump inhibitors, on these colistin-resistant strains. Using the broth microdilution method, a CO and CCCP combination of 2 mu g/mL and 10 mu g/mL, respectively, significantly reduced the CO minimal inhibitory concentration (MIC) of B. intermedia, supporting an efflux pump mechanism. In contrast, VRP, PA beta N and RSP did not restore CO susceptibility. A time kill assay showed a bactericidal effect of the CO-CCCP combination. Genomic analysis revealed a potential implication in the CO resistance mechanism of some conserved efflux pumps, such as YejABEF, NorM and EmrAB, as previously reported in other bacteria. An inhibitory effect of the CO-CCCP combination was observed on biofilm formation using the crystal violet method. These results suggest that the intrinsic CO resistance in Brucella intermedia is linked to an efflux pump mechanism and that the synergistic effect of CO-CCCP may open a new field to identify new treatments to restore antibiotic efficacy in humans.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Santé : généralités [050]
;
Biotechnologies [084]
