Antibiotic adjuvants to rescue Pseudomonas aeruginosa from tetracycline antibiotics resistance
Résumé
An attractive antibiotic-adjuvant strategy consisting in the design and synthesis of polyaminoisoprenyl molecules able to restore antibiotic activity of tetracycline antibiotics against resistant Pseudomonas aeruginosa bacterial strains has been developed. These chemosensitizers are readily prepared from geraniol and farnesol in an efficient two steps synthesis with good to moderate yields varying from 38 to 64% and leading to a significant decrease of antibiotic resistance. Thus, the influence of the nature of the tetracycline antibiotic used as well as the structure of the polyaminoisoprenyl derivatives involved on the outcome of the antibiotic-adjuvant combination against P. aeruginosa resistance to tetracyclines were investigated. Additionally, our data suggested that their mechanism of action is closely associated with the increase of the outer-membrane permeability.
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