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Carbonyl Cyanide 3-Chloro Phenyl Hydrazone (CCCP) Restores the Colistin Sensitivity in Brucella intermedia
- Source :
- International Journal of Molecular Sciences, Volume 24, Issue 3, Pages: 2106, International Journal of Molecular Sciences, 2023, 24 (3), pp.2106. ⟨10.3390/ijms24032106⟩
- Publication Year :
- 2023
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2023.
-
Abstract
- 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 β-naphthylamide dihydrochloride (PAβN) 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 µg/mL and 10 µg/mL, respectively, significantlyreduced the CO minimal inhibitory concentration (MIC) of B. intermedia, supporting an efflux pump mechanism. In contrast, VRP, PAβN 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.
- Subjects :
- [SDV]Life Sciences [q-bio]
Organic Chemistry
synergy
General Medicine
intrinsic colistin resistance
Catalysis
Computer Science Applications
Inorganic Chemistry
carbonyl cyanide 3-chloro phenyl hydrazone
CO-MIC
biofilm formation
efflux pump
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
efflux pump inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 14220067 and 16616596
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....67a6e0aaeaf51cbdf3daf298ae90bb7b
- Full Text :
- https://doi.org/10.3390/ijms24032106