%0 Journal Article
%T Use of Poly (-Lysine) Dendrons: A Strategy Targeting Bacterial Quorum Sensing and Biofilm Formation
%A Rahaf Issa
%A Steve T. Meikle
%A Stuart L. James
%A Ian R. Cooper
%J Conference Papers in Science
%D 2014
%R 10.1155/2014/572828
%X 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 ( -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 ( -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. 1. Introduction 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 ¡ê1 billion per annum [2]. Among the most prevalent human pathogens noted for antibiotic resistance is Pseudomonas aeruginosa. This Gram-negative, opportunistic bacterium accounts for an estimated 6% of all nosocomial infection reports [1] and is also the primary cause of respiratory deterioration and mortality in patients with cystic fibrosis [3, 4]. The ability of many pathogens to negate the effects of antibiotics is mediated in part by the formation of surface-attached, 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 therefore protects underlying organisms from external stresses (such as antibiotic penetration) [6]. Given the latter, it is not surprising that approximately 65% of all human bacterial infections involve biofilms [7]. Furthermore, biofilms regularly impede
%U http://www.hindawi.com/journals/cpis/2014/572828/