Artemisia herba-alba Asso and Cymbopogon citratus (DC.) Stapf essential oils and their capability to restore antibiotics efficacy

• Antibacterial activity of Artemisia herba-alba and Cymbopogon citratus EOs and their ability to restore antibiotics efficacy have been investigated.
• Active compounds of studied EOs could be substrates of the efflux pumps of tested strains.
• Lipopolysaccharide is involved in the resistance to the active compounds of studied EOs in Salmonella strains.
• Studied EOs can block efflux pumps and may be good candidates to develop new drugs able to restore antibiotic activity of some MDR Gram-negative bacteria.

Inhibition of bacterial efflux mechanisms has been investigated as a promising target to combat the bacterial resistance to antibiotics. The present work investigated the ability of Artemisia herba-alba and Cymbopogon citratus essential oils (EOs) to inhibit efflux pumps of some selected antibiotic-resistant Gram-negative bacteria. The chemical profiles of tested EOs were evaluated by GC–MS. The major constituents of the oils were chrysanthenone (47.0%), camphor (24.0%), and verbenone (7.2%) in A. herba-alba EO and geranial (46.3%), neral (35.2%), and geraniol (5.4%) in C. citratus EO. Antibacterial tests showed that these EOs had high antibacterial activity. This activity was significantly enhanced in the presence of an efflux pump inhibitor, phenylalanine arginyl ß-naphthylamide (PAßN). When combined with PAßN, the MIC values against EA27 and AG102 (strains overexpressing efflux pumps) were decreased 32-fold and >32-fold, respectively, for A. herba-alba, and 512-fold and 1024-fold, respectively, for C. citratus EO. The involvement of a lipopolysaccharide (LPS) structure in the resistance to the active compounds of the studied EOs was also demonstrated in Salmonella LPS deep-rough mutants. Moreover, the combination of A. herba-alba and C. citratus EOs, at a low concentration, reduced significantly chloramphenicol MIC 2–4-fold, 4-fold and 8–16-fold, respectively, for EAEP294 (deleted of AcrAB), EA27 and AG102. For Salmonella strains, all tested combinations recorded a gain greater than or equal to 64-fold. It was concluded that these EOs can alter efflux pump activity and may be good candidates for the development of new chemosensitizer drugs able to restore antibiotic activity of some drug-resistant Gram-negative bacteria.