6533b836fe1ef96bd12a0c28

RESEARCH PRODUCT

Cinnamaldehyde Induces Expression of Efflux Pumps and Multidrug Resistance in Pseudomonas aeruginosa

Corine GirardAndy ZedetPatrick PlésiatAlexandre TetardCatherine Llanes

subject

medicine.drug_classAntibioticsMicrobial Sensitivity Testsmedicine.disease_causeCinnamaldehydeMicrobiology03 medical and health scienceschemistry.chemical_compoundAntibiotic resistanceMechanisms of ResistanceDrug Resistance Multiple BacterialOils VolatilemedicineTobramycin[CHIM]Chemical SciencesPharmacology (medical)AcroleinComputingMilieux_MISCELLANEOUS030304 developmental biologyPharmacology0303 health sciences030306 microbiologyPseudomonas aeruginosaMembrane Transport Proteins[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biologybiochemical phenomena metabolism and nutrition[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciencesAnti-Bacterial Agents3. Good healthCiprofloxacinMultiple drug resistanceInfectious DiseaseschemistryPseudomonas aeruginosaEffluxmedicine.drug

description

Essential oils or their components are increasingly used to fight bacterial infections. Cinnamaldehyde (CNA), the main constituent of cinnamon bark oil, has demonstrated interesting properties in vitro against various pathogens, including Pseudomonas aeruginosa. In the present study, we investigated the mechanisms and possible therapeutic consequences of P. aeruginosa adaptation to CNA. Exposure of P. aeruginosa PA14 to subinhibitory concentrations of CNA caused a strong albeit transient increase in the expression of operons that encode the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY/OprM. This multipump activation enhanced from 2- to 8-fold the resistance (MIC) of PA14 to various antipseudomonal antibiotics, including meropenem, ceftazidime, tobramycin, and ciprofloxacin. CNA-induced production of pump MexAB-OprM was found to play a major role in the adaption of P. aeruginosa to the electrophilic biocide, through the NalC regulatory pathway. CNA was progressively transformed by bacteria into the less toxic metabolite cinnamic alcohol (CN-OH), via yet undetermined detoxifying mechanisms. In conclusion, the use of cinnamon bark oil or cinnamaldehyde as adjunctive therapy to treat P. aeruginosa infections may potentially have antagonistic effects if combined with antibiotics because of Mex pump activation.

10.1128/aac.01081-19https://hal.archives-ouvertes.fr/hal-02538771