Journal article

Investigating the Interaction of Octapeptin A3 with Model Bacterial Membranes

Mei-Ling Han, Hsin-Hui Shen, Karl A Hansford, Elena K Schneider, Sivashangarie Sivanesan, Kade D Roberts, Philip E Thompson, Anton P Le Brun, Yan Zhu, Marc-Antoine Sani, Frances Separovic, Mark AT Blaskovich, Mark A Baker, Samuel M Moskowitz, Matthew A Cooper, Jian Li, Tony Velkov

ACS INFECTIOUS DISEASES | AMER CHEMICAL SOC | Published : 2017

Abstract

Octapeptins are cyclic lipopeptides with a broader spectrum of activity against fungi and polymyxin-resistant Gram-negative and Gram-positive bacteria. In the present study, we investigated the interaction of octapeptin A3 with asymmetric outer membrane models of Gram-negative pathogen Pseudomonas aeruginosa using neutron reflectometry, together with fluorimetric and calorimetry methods. For the first time, our neutron reflectometry results reveal that the interaction of octapeptin A3 with the Gram-negative outer membrane involves an initial transient polar interaction with the phospholipid and lipid A headgroups, followed by the penetration of the entire octapeptin molecule into the fatty a..

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Grants

Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health


Awarded by NIH


Awarded by NHMRC


Awarded by ANSTO


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

J.L. and T.V. are supported by research grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01A1070896 and R01AI079330). J.L., T.V., H.-H.S., and M.A.C. are also supported by the Australian National Health and Medical Research Council (NHMRC) M.A.B and K.H. are supported by grants from NIH (R21AI098731/R33AI098731) and NHMRC (APP1005350 and APP1045326). 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. The authors would like to thank AINSE and ANSTO for the financial support (awards of neutron beam time P4787 and AINSE-PGRA)