Project description:This study aims to determine the global gene expression in vancomycin resistant Enterococcus faecium (VRE) in response to a novel essential oil-vancomycin combination, and the individual components (vancomycin, carvacrol and cuminaldehyde) to help determine the mechanism of action of this antimicrobial formulation. This formulation increases the susceptibility of VRE to vancomycin and the array provides data on the synergistic mechanism of action. Five conditions (1. Control; 2. Carvacrol, 1.98 mM; 3. Cuminaldehyde, 4.20 mM; 4. Vancomycin, 0.031 mg/l; 5. Combination, 1.98 mM Carvacrol, 4.2 mM Cuminaldehyde, 0.031 mg/l vancomycin) all with 1% DMSO were tested in triplicate with a 60 minute exposure time before extraction.
Project description:The emergence of multi-drug resistant pathogens is a major public health problem, leading to rethink and innovate in our bacterial control strategies. Here, we explore the anti-biofilm and anti-virulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain, on 4 major pathogens, i.e. carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), a methicillin-resistant S. aureus (MRSA) and a vancomycin-resistant E. faecium (VRE) strains. We screened the effect of these derivatives on biofilm formation and eradication. 4e (for CRAB, VRE and MRSA) and 4f (for all the strains) were the most potent one and displayed activities as good as conventional antibiotics. We also identified 11 compounds able to decrease by more than 40% the production of pyocyanin, a major virulence factor of P. aeruginosa. We demonstrated that 4f treatment acts against bacterial infections in Galleria mellonella and significantly prolonged the larvae survival (from 50% to 80%) after 24 h of CRAB, VRE and MRSA infections. As shown by proteomic studies, 4f triggered distinct cellular responses depending on the bacterial species, but essentially related to the cell envelop. Its interesting anti-biofilm and anti-virulence properties make it promising candidate for use in therapeutics.
