Journal article
Molecular basis for the increased polymyxin susceptibility of Klebsiella pneumoniae strains with under-acylated lipid A
T Velkov, RL Soon, PL Chong, JX Huang, MA Cooper, MAK Azad, MA Baker, PE Thompson, K Roberts, RL Nation, A Clements, RA Strugnell, J Li
Innate Immunity | Published : 2013
Abstract
The impact of under-acylation of lipid A on the interaction between Klebsiella pneumoniae LPS and polymyxins B and E was examined with fluorometric and calorimetric methods, and by 1H NMR, using a paired wild type (WT) and the ΔlpxM mutant strains B5055 and B5055ΔlpxM, which predominantly express LPS with hexa- and penta-acylated lipid A structures respectively. LPS from B5055ΔlpxM displayed a fourfold increased binding affinity for polymyxins B and E compared with the B5055 WT LPS. EC50 values were consistent with polymyxin minimum inhibitory concentration (MIC) values for each strain. Accordingly, polymyxin exposure considerably enhanced the permeability of the B5055ΔlpxM OM. Analysis of t..
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Funding Acknowledgements
[ "R. L. N. and J. L. are supported by research grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01A1070896 and R01AI079330). T. V., R. L. N., J. L., P. E. T. and K. R. are also supported by the Australian National Health and Medical Research Council (NHMRC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.", "J. L. is an Australian NHMRC Senior Research Fellow. T. V. and M. A. B. are Australian NHMRC Career Development Research Fellows. M. C. is a NHMRC Australia Fellow supported by AF511105." ]