Zoaiter M. auteur aut IRD Zeaiter Z. auteur aut IRD Mediannikov Oleg auteur aut IRD Sokhna Cheikh auteur aut IRD Fournier P. E. auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized intrinsic colistin resistance efflux pump inhibitors carbonyl cyanide 3-chloro phenyl hydrazone CO-MIC synergy efflux pump biofilm formation 020 050 084 24 3 2106 [14 ] 2023 https://www.documentation.ird.fr/hor/fdi:010086923 10.3390/ijms24032106 [F B010086923] https://www.documentation.ird.fr/hor/fdi:010086923 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2023-03/010086923.pdf IRD - Base Horizon / Pleins textes 2023-03-08 2025-02-24 fdi:010086923 fre