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Antibiofilm and antivirulence properties of 6-polyaminosteroid derivatives against antibiotic-resistant bacteria

ABSTRACT: 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.

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Cecile Muller

PROVIDER: PXD048020 | iProX | Wed Dec 20 00:00:00 GMT 2023

REPOSITORIES: iProX

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Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria.

Vergoz Delphine D Le Hung H Bernay Benoit B Schaumann Annick A Barreau Magalie M Nilly Flore F Desriac Florie F Tahrioui Ali A Giard Jean-Christophe JC Lesouhaitier Olivier O Chevalier Sylvie S Brunel Jean Michel JM Muller Cécile C Dé Emmanuelle E

Antibiotics (Basel, Switzerland) 20231220 1

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain on four major pathogens, i.e., carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), methicillin-resistant S. aureus (MRSA), and vancomyc ...[more]

PMID: 38275318

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Project description:Intercellular signal indole and its derivative hydroxyindoles inhibit Escherichia coli biofilm and diminish Pseudomonas aeruginosa virulence. However, indole and bacterial indole derivatives were unstable in microbial community due to the widespread of diverse oxygenases that could quickly degrade them. Hence, we sought to identify novel non-toxic, stable, and potent indole derivatives from plant sources for inhibiting biofilm formation of E. coli O157:H7 and P. aeruginosa PAO1. Here, plant auxin 3-indolylacetonitrile (IAN) was found to inhibit biofilm formation of both E. coli O157:H7 and P. aeruginosa without affecting its growth. IAN inhibited biofilms more effectively than indole for both E. coli and P. aeruginosa. Additionally, IAN decreased the production of virulence factor pyocyanin in P. aeruginosa. DNA microarray analysis indicated that IAN repressed genes involved in curli formation and glycerol metabolism, while IAN induced indole-related genes and prophage genes in E. coli. It appears that IAN inhibits biofilm formation of E. coli by reducing curli formation and inducing indole production. Furthermore, unlike bacterial indole derivatives, plant-originated IAN was stable in the presence of either E. coli or P. aeruginosa. For the microarray experiments, P. aeruginosa were inoculated in 25 ml of LB medium in 250 ml shake flasks with overnight cultures that were diluted 1:100. IAN (100 μg/ml) dissolved in 25 μl DMSO or 25 μl DMSO alone as a control was added. Cells were cultured in LB at 37C with 250 rpm shakingfor 5 hrs. Cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 sec before centrifugation in 50 ml centrifuge tubes at 13,000 g for 2 min; cell pellets were frozen immediately with dry ice and stored -80°C. RNA was isolated using Qiagen RNeasy mini Kit (Valencia, CA, USA). RNA quality was assessed by Agilent 2100 bioanalyser using the RNA 6000 Nano Chip (Agilent Technologies, Amstelveen, The Netherlands), and quantity was determined by ND-1000 Spectrophotometer (NanoDrop Technologies, Inc., DE, USA).

Dataset Information

Antibiofilm and antivirulence properties of 6-polyaminosteroid derivatives against antibiotic-resistant bacteria

Publications

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria.

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