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O'Driscoll PhD thesis.pdf14.22 MBAdobe PDFView/Open
Title: Investigation into the antimicrobial activity of cationic antibacterials.
Authors: O'Driscoll, Noelle H.
Supervisors: Lamb, Andrew
Matthews, Kerr H.
Mercer, Derry
Issue Date: Aug-2011
Publisher: Robert Gordon University
Abstract: The topic addressed by the 2011 WHO‘s World Health Day was antibacterial resistance. This action served to highlight the serious problem bacterial resistance now presents to healthcare professionals globally. This investigation focussed on the action of four cationic antimicrobial agents against E. coli, S. aureus and P. aeruginosa. Triclosan is widely used clinically and as an ingredient of personal care products that has come under renewed scrutiny by the FDA last year. Colistin is used clinically as salvage therapy against multi-drug resistant bacteria, particularly P. aeruginosa and A. baumanii. NP101 and NP108 are novel antimicrobial peptides, considered as a class with huge future potential in the treatment of not only bacterial but also viral and fungal infections in humans. The action of triclosan on all three test bacteria, including P. aeruginosa, historically considered resistant to triclosan, revealed concentration dependent bacteriostatic/bactericidal effects; reduction in bacterial growth; inhibition of second-phase logarithmic growth in S. aureus; induction of minimal K+ loss in all bacterial species; non-septation and aggregation in all test species. Colistin use was abandoned clinically between 1970-2000 and is not used clinically against Gram-positive species. Colistin exposure induced a common response from test bacteria including the Gram-positive S. aureus; concentration dependent retardation in onset of bacterial growth, without reduction in final bacterial density; significant K+ loss from S. aureus and E. coli but not P. aeruginosa; the development of resistance to the inhibitory colistin concentration by P. aeruginosa and S. aureus but not E. coli; production of small colony variants by P. aeruginosa; formation of spherical aggregates; membrane blebbing and inhibition of normal bacterial septation. Similar responses to NP101 and NP108 were observed to the test bacteria; an all or nothing effect on bacterial growth; prevention of second phase logarithmic growth in S. aureus; induction of significant K+ loss in all bacteria; size and shape alterations; extrusion of intracellular material, membrane blebbing; inhibition of bacterial septation and interruption of binary fission. Each of these peptides was incorporated into lyophilised wafers and tested for in vitro topical antibacterial efficacy and shown to have antibacterial activity against all test species.
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