Polyamino-isoprenyl derivatives as antibiotic adjuvants and motility inhibitors for 1 Bordetella bronchiseptica porcine pulmonary infection treatment 2 3

Diane Borselli (1, 2) , Jean Michel Brunel (1, 2) , Olivier Gorgé (1, 2) , Jean Michel Bolla (1, 2)

1 IRBA - Institut de Recherche Biomédicale des Armées [Antenne Marseille]
2 MCT - Membranes et cibles thérapeutiques

The spreading of multidrug-resistant bacteria and the lack of novel antibiotic molecules leave clinicians and veterinarians with very limited options to treat bacterial infections, especially those caused by Gram-negative pathogens. To reduce the selection of antibiotic resistance mechanisms and their transfer to human pathogens, veterinary pharmaceutical companies have dramatically decreased the number of antibiotics used. Among all the investigated alternate solutions, chemosensitizers, which decrease the amount of the used drugs, appear to be one of the most promising strategies. In this study, we reported that polyamino-isoprenyl derivatives can potentiate florfenicol activity against veterinary sensitive reference strains as well as clinical isolates. These molecules induce inner membrane depolarization and subsequently inhibit efflux pumps by collapsing the proton-motive force (PMF). Considering that Bordetella bronchiseptica rotor flagellum is highly PMF dependent and that flagellar motility represents an important factor involved in colonization, we monitored the swimming and swarming motilities of bacteria and showed a strong inhibition in the presence of the lead selected compound. Taken together, our results suggest that this class of molecules are able to increase treatment efficacy and decrease drug consumption.

Mots clés: Antibiotic resistance; Combination therapy; Whole-cell screening; motility; 12 virulence; Bordetella bronchiseptica 13

Domaines: Chimie; Chimie organique; Sciences du Vivant [q-bio]; Microbiologie et Parasitologie; Bactériologie

Diane Borselli, Jean Michel Brunel, Olivier Gorgé, Jean Michel Bolla. Polyamino-isoprenyl derivatives as antibiotic adjuvants and motility inhibitors for 1 Bordetella bronchiseptica porcine pulmonary infection treatment 2 3. Frontiers in Microbiology, 2019, 10, ⟨10.3389/fmicb.2019.01771⟩. ⟨hal-02392731⟩