Journal article

A nanomechanical study of the effects of colistin on the Klebsiella pneumoniae AJ218 capsule

A Mularski, J Wilksch, E Hanssen, J Li, T Tomita, SJ Pidot, T Stinear, F Separovic, D Strugnell

European Biophysics Journal | SPRINGER | Published : 2017

Abstract

Atomic force microscopy measurements of capsule thickness revealed that that the wild-type Klebsiella pneumoniae AJ218 capsular polysaccharides were rearranged by exposure to colistin. The increase in capsule thickness measured near minimum inhibitory/bactericidal concentration (MIC/MBC) is consistent with the idea that colistin displaces the divalent cations that cross-bridge adjacent lipopolysaccharide (LPS) molecules through the capsule network. Cryo-electron microscopy demonstrated that the measured capsule thickness at near MIC/MBC of 1.2 μM was inflated by the disrupted outer membrane, through which the capsule is excreted and LPS is bound. Since wild-type and capsule-deficient strains..

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Grants

Awarded by National Institutes of Health


Funding Acknowledgements

The authors gratefully acknowledge the support of the Australian Research Council and the National Health and Medical Research Council (Program Grant 606788) and Dr. Michelle Gee, who together with JL, initially suggested the AFM study of the effect of colistin on K. pneumoniae. AM received an Australian Postgraduate Award and a David Hay Postgraduate Writing-Up Award. JL is an Australian NHMRC Senior Research Fellow and is supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965). 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. All AFM work was conducted at the Nanomaterials Platform, University of Melbourne. Electron microscopy was carried out at the Bio21 Advanced Microscopy Facility, University of Melbourne.