Antibiotic Adjuvants: Make Antibiotics Great Again!

Hana Douafer (1) , Véronique Andrieu (2) , Otto Phanstiel (3) , Jean Michel Brunel (1)

1 MCT - Membranes et cibles thérapeutiques
2 MEPHI - Microbes évolution phylogénie et infections
3 UCF - University of Central Florida [Orlando]

During the last decades, multiple approaches have been developed to combat bacterial resistance. However, the combination of antibiotic resistance mechanisms by bacteria and the limited number of effective antibiotics available, decreases the number of the interventions for the treatment of current bacterial infections. The solution to emerging antibiotic resistance will likely involve combination therapies of existing antibiotics and smart adjuvants, which re-empower the antibiotic agent to become efficacious against the resistant strain of interest. In this context, amphiphatic molecules provide the opportunity to target difficult-to-traverse bacterial membranes. We will depict herein that a reasoned adjuvant design permits to perform polypharmacy on bacteria by not only providing greater internal access to the co-dosed antibiotics but also by de-energizing the efflux pumps used by the bacteria to escape antibiotic action.

Mots clés: Inhibitors; Antibiotic resistance; Antimicrobial agents; Bacteria; Membranes

Domaines: Bactériologie; Virologie; Parasitologie; Cardiologie et système cardiovasculaire; Maladies émergentes; Maladies infectieuses

Hana Douafer, Véronique Andrieu, Otto Phanstiel, Jean Michel Brunel. Antibiotic Adjuvants: Make Antibiotics Great Again!. Journal of Medicinal Chemistry, 2019, 62 (19), pp.8665-8681. ⟨10.1021/acs.jmedchem.8b01781⟩. ⟨hal-02262519⟩