Poly(ε-lysine) dendrons as modulators of quorum sensing in Pseudomonas aeruginosa. 2015

Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK, r.issa1@uni.brighton.ac.uk.

The opportunistic pathogen Pseudomonas aeruginosa is a significant contributor to recalcitrant multi-drug resistant infections. In a vigorous search for alternative therapeutic approaches, the communication system used by this bacterium to synchronise the expression of genes involved in pathogenicity has been identified as a potential target. Poly(ε-lysine) dendrons, composed of three branching generations, were examined herein for their anti-virulence potential and ability to disperse within P. a eruginosa biofilms. These hyperbranched macromolecules reduced attachment and biomass production under different nutrient growth conditions, and at concentrations that were not lethal to planktonic cells (0.2, 0.4 and 0.8 mg/mL). Fluorescent labelling revealed the intracellular localisation and cell-penetrating capacity of the dendron, and showed the rapid uptake and release of unexploited dendron from pre-established P. a eruginosa biofilms. Additionally, the dendron induced complete attenuation of LasA protease, a marker of quorum sensing inactivation, by preventing its accumulation in the external environment. This study thus demonstrates the anti-virulence potential of this class of macromolecules, and could represent a novel therapeutic approach for the treatment of antibiotic-resistant P. a eruginosa infections.

UI MeSH Term Description Entries
D008422 Materials Testing The testing of materials and devices, especially those used for PROSTHESES AND IMPLANTS; SUTURES; TISSUE ADHESIVES; etc., for hardness, strength, durability, safety, efficacy, and biocompatibility. Biocompatibility Testing,Biocompatible Materials Testing,Hemocompatibility Testing,Testing, Biocompatible Materials,Testing, Hemocompatible Materials,Hemocompatibility Testings,Hemocompatible Materials Testing,Materials Testing, Biocompatible,Materials Testing, Hemocompatible,Testing, Biocompatibility,Testing, Hemocompatibility,Testing, Materials,Testings, Biocompatibility
D011107 Polylysine A peptide which is a homopolymer of lysine. Epsilon-Polylysine,Poly-(Alpha-L-Lysine),Epsilon Polylysine
D011550 Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D050091 Dendrimers Tree-like, highly branched, polymeric compounds. They grow three-dimensionally by the addition of shells of branched molecules to a central core. The overall globular shape and presence of cavities gives potential as drug carriers and CONTRAST AGENTS. Dendrimer,Dendritic Compounds,Dendritic Polymers,Dendrons,Compound, Dendritic,Dendritic Compound,Dendritic Polymer,Polymer, Dendritic,Polymers, Dendritic
D053038 Quorum Sensing A phenomenon where microorganisms communicate and coordinate their behavior by the accumulation of signaling molecules. A reaction occurs when a substance accumulates to a sufficient concentration. This is most commonly seen in bacteria. Quorum Quenching,Quenching, Quorum,Quenchings, Quorum,Quorum Quenchings,Sensing, Quorum
D018441 Biofilms Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an EXTRACELLULAR POLYMERIC SUBSTANCE MATRIX that is secreted by the microbes. They occur on body surfaces such as teeth (DENTAL DEPOSITS); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and anti-fouling agents. Biofilm

Related Publications

Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
January 2021, Current topics in medicinal chemistry,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
January 2022, Advances in experimental medicine and biology,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
February 2009, Environmental microbiology,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
January 2018, Frontiers in cellular and infection microbiology,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
August 2008, Applied microbiology and biotechnology,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
May 2018, Biotechnology letters,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
December 2005, FEMS microbiology letters,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
May 2017, Organic & biomolecular chemistry,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
November 2003, The Journal of clinical investigation,
Rahaf Issa, and Steve T Meikle, and Stuart James, and Ian R Cooper
January 2005, Critical reviews in microbiology,
Copied contents to your clipboard!