Interaction of a novel quinolone analogue with model bacterial membranes
Persistent infections caused by non-reproducing bacteria are very difficult to treat with conventional metabolism-targetting antibiotics, because the cells are metabolically inert. This allows opportunistic pathogens such as Staphylococcus aureus to cause chronic colonisation and infections, which are a major problem for long-term hospital patients. HT61 is a novel quinolone analogue which has been shown to act preferentially against non-reproducing bacteria, and therefore shows promise as a therapeutic weapon against recalcitrant infections caused by S. aureus. Although the mode of action of HT61 is as yet unknown, evidence suggests that it may act through a membrane-disrupting mechanism, since it has been shown to depolarise S. aureus cell membranes, and to partition into bacterial-mimetic anionic monolayers at the air/water interface. We propose a neutron reflectometry experiment to determine the degree to which the membrane partitioning of HT61 may alter lipid bilayer parameters to be consistent with the observed cell depolarisation. This will provide important data for the elucidation of this novel antibiotic's bactericidal mechanism.
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Richard D. Harvey; BARKER Robert; HUBBARD Alasdair and REHAL Reg. (2012). Interaction of a novel quinolone analogue with model bacterial membranes. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-653
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