LENS Webinar #5, Global Health Threats: Microbial resistance and novel antibiotics

Prof. Jeremy Lakey: Studying the surfaces of bacteria using neutron scattering. Finding new openings for antibiotics

Prof. Martin Malmsten: Antimicrobial peptides – from membrane interactions to drug delivery

08 October 2020, 11:00am CET

Chair: John Webster, ISIS neutron and muon facility

Prof Jeremy Lakey is currently Professor of Structural Biochemistry at Newcastle University Medical School, UK and has been interested in bacterial membranes and antibiotics since his PhD. In 2002 he was awarded a BBSRC Research Development Fellowship to investigate the nanoscale structure of both natural membranes and synthetic interfaces based upon engineered proteins. One technique he chose was neutron reflectometry and so he began a steep learning curve for a biologist! Since then collaborations with Stephen Holt and Luke Clifton have enabled his group to develop some very powerful neutron-based approaches to understanding bacterial membrane structure and function.

The use of neutrons as a scattering probe to investigate biological membranes has steadily grown in the past three decades, shedding light on the structure and behaviour of this ubiquitous and fundamental biological barrier. Meanwhile, the rise of antibiotic resistance has catalysed a renewed interest in understanding the mechanisms underlying the dynamics of antibiotics interaction with the bacterial cell envelope. It is widely recognised that the key reason behind the remarkable success of Gram-negative pathogens in developing antibiotic resistance lies in the effectiveness of their outer membrane (OM) in defending the cell from antibacterial compounds. In this talk I will discuss the opportunities offered by neutron scattering techniques, in particular reflectometry, to provide structural information on the interactions of antimicrobials with in vitro models of the OM.

Prof. Martin Malmsten is professor in Biopharmaceuticals, Biophysics, and Drug Delivery, as well as Director of the LEO Foundation Center for Cutaneous Drug Delivery, at the University of Copenhagen. Editor-in-Chief of the Journal of Colloid and Interface Science. Malmstens current research interests include nanomaterials for drug delivery, as well as amphiphilic peptide therapeutics.

Membrane interactions play an important role for host defense peptides, including their antimicrobial, anti-inflammaory, and anticancer effects. The present overview exemplifies some of our work on how biophysical investigations with model lipid bilayers and bacterial lipopolysaccharides can be combined with biological experiments to clarify modes-of-action, and allow peptide optimization towards therapeutic development.

In addition, since efficient delivery of such peptides is challenging due to their size, cationicity, and amphiphilicity, delivery systems are important for their development into therapeutics, e.g., for controlling peptide release, for reducing infection-related peptide degradation, for suppression of toxicity, or for increasing bioavailability. Reporting on some of our recent work in this area, membrane interactions and antimicrobial effects of selected nanomaterials as peptide delivery systems are outlined, ranging from nanoparticles as passive peptide containers to systems providing additional functions for combatting infection.

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