Abstract
Pseudomonas aeruginosa is recognised as a major aetiological agent of nosocomial infections, which are associated with multiple-antibiotic resistance. Among many of its important virulence factors is its ability to form biofilms on the surfaces of implantable medical devices and to produce toxic metabolites, pyocyanin, via an intercellular cell density-dependent signalling system of communication. In this study, poly (ε-lysine) dendrons composed of increasingly branching generations were synthesised, characterised, and examined for their effects on virulence factor production in P. aeruginosa. The results show that these hyperbranched poly (ε-lysine) dendrons, in particular the 3rd generation, can increase the efficacy of a conventional antibiotic, ciprofloxacin, and reduce pyocyanin production, with marginal effects on the rate of bacterial replication, suggesting that the observed effects are not due to dendron toxicity. Furthermore, dendron and ciprofloxacin coadministration was identified as the most effective strategy which highlights the potential of peptide-based dendrons as quorum sensing inhibitors.
Highlights
The emergence of multiple-antibiotic resistant bacterial strains is one of the greatest contemporary challenges in modern medical science and is increasing at a rate that far exceeds the pace of the development of new drugs [1, 2]
Subcultures were prepared from these stocks, where cells were maintained on nutrient agar (NA) plates and in nutrient broth (NB) (Oxoid, UK) to produce overnight cultures at 37∘C with agitation
Dendrons became increasingly branched in line with the generation number, exposing a large number of functional amine groups on the outermost branching generation (Figures 1(a)–1(c))
Summary
The emergence of multiple-antibiotic resistant bacterial strains is one of the greatest contemporary challenges in modern medical science and is increasing at a rate that far exceeds the pace of the development of new drugs [1, 2] This rise in antimicrobial resistance allows infections to develop into chronic conditions, which are estimated to account for approximately 25,000 excess mortalities in the EU annually and cost the national healthcare providers in excess of £1 billion per annum [2]. The ability of many pathogens to negate the effects of antibiotics is mediated in part by the formation of surfaceattached, structured communities of bacterial cells through a process termed biofilm formation [5] The development of these microbial communities has been shown to provide an altered microenvironment, whereby an intrinsic physical barrier is formed which protects underlying organisms from external stresses (such as antibiotic penetration) [6]. Biofilms regularly impede the ability of medical implants to function, which results in device failure [8]
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