{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:09:55Z","timestamp":1791846595511,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut Hospitalo-Universitaire mediterranee-infection"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats: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 \u03b2-naphthylamide dihydrochloride (PA\u03b2N) 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 \u00b5g\/mL and 10 \u00b5g\/mL, respectively, significantly\u00a0reduced the CO minimal inhibitory concentration (MIC) of B. intermedia, supporting an efflux pump mechanism. In contrast, VRP, PA\u03b2N and RSP did not restore CO susceptibility. A time kill assay showed a bactericidal effect of the CO\u2013CCCP 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\u2013CCCP 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\u2013CCCP may open a new field to identify new treatments to restore antibiotic efficacy in humans.<\/jats:p>","DOI":"10.3390\/ijms24032106","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Carbonyl Cyanide 3-Chloro Phenyl Hydrazone (CCCP) Restores the Colistin Sensitivity in Brucella intermedia"],"prefix":"10.3390","volume":"24","author":[{"given":"Malak","family":"Zoaiter","sequence":"first","affiliation":[{"name":"Institut Hospitalo-Universitaire M\u00e9diterran\u00e9e-Infection, 13005 Marseille, France"},{"name":"Institut de Recherche pour le d\u00e9veloppement (IRD), Assistance publique des h\u00f4pitaux de Marseille (AP-HM), SSA, Vecteurs Infections Tropicales et M\u00e9diterran\u00e9ennes (VITROME), Aix-Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaher","family":"Zeaiter","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, Lebanese University LU, Beirut 146404, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-2008","authenticated-orcid":false,"given":"Oleg","family":"Mediannikov","sequence":"additional","affiliation":[{"name":"Institut Hospitalo-Universitaire M\u00e9diterran\u00e9e-Infection, 13005 Marseille, France"},{"name":"Institut de Recherche pour le d\u00e9veloppement (IRD), Assistance publique des h\u00f4pitaux de Marseille (AP-HM), Microbes, Evolution, Phylog\u00e9nie et Infection (MEPHI), Aix-Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheikh","family":"Sokhna","sequence":"additional","affiliation":[{"name":"Institut Hospitalo-Universitaire M\u00e9diterran\u00e9e-Infection, 13005 Marseille, France"},{"name":"Institut de Recherche pour le d\u00e9veloppement (IRD), Assistance publique des h\u00f4pitaux de Marseille (AP-HM), Microbes, Evolution, Phylog\u00e9nie et Infection (MEPHI), Aix-Marseille Universit\u00e9, 13005 Marseille, France"},{"name":"Campus Commun UCAD-IRD of Hann, Dakar 1020, Senegal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Edouard","family":"Fournier","sequence":"additional","affiliation":[{"name":"Institut Hospitalo-Universitaire M\u00e9diterran\u00e9e-Infection, 13005 Marseille, France"},{"name":"Institut de Recherche pour le d\u00e9veloppement (IRD), Assistance publique des h\u00f4pitaux de Marseille (AP-HM), SSA, Vecteurs Infections Tropicales et M\u00e9diterran\u00e9ennes (VITROME), Aix-Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1146\/annurev.bi.46.070177.003451","article-title":"Polymyxin and Related Peptide Antibiotics","volume":"46","author":"Storm","year":"1977","journal-title":"Annu. 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