Action of Polymyxin B on Bacterial Membranes, I. Binding to the O-Antigenic Lipopolysaccharide of Salmonella typhimurium
2014
Bader, J. | Teuber, M.
Polymyxin B (PX) forms complexes with the O-antigenic lipopolysaccharide (LPS) of Salmonella typhimurium which are stable in aqueous 0.14 ᴍ sodium chloride at neutral pH. PX can be quantitatively recovered from the complex by changing the pH from 7 to 1, or by treatment with the cationic detergent cetylpyridinium chloride. This proves that complex formation does not involve covalent linkages, but is due to electrostatic, and possibly hydrophobic interactions. Quantitative investigations of the binding properties of mutant LPS of the chemotype Rc and Re, of degraded polysaccharide and isolated lipid A point to the negatively charged ketodeoxyoctonate-lipid A region of LPS as binding site for PX. These biochemical results are confirmed by a blueshift of the fluorescence emission maximum of LPS-bound mono-Ar-dimethylaminonaphthalenesulfonyl PX from 550 to 515 nm which corresponds to a location of the dansyl-PX at a polar-apolar interface³⁴. Using a published molecular weight of the Rc LPS of 10 000²⁹, it is calculated that one LPS molecule can bind 2.7 molecules PX. It is discussed that the PX-LPS interaction may be necessary to alter the permeability of the outer membrane which is a prerequisite for the antibiotic to gain access to it’s final target, the cytoplasmic membrane.
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