Last-resort antibiotics prepare E. coli membranes for disruption

Polymyxins are considered last-resort antibiotics which are still effective against multi-drug resistant pathogens. In a study published by Nature Communications, Selen Manioglu and colleagues from the Biophysics group and the Biozentrum, University of Basel, now describe their mechanistic effect at the molecular level. Using atomic force microscopy imaging, the results show that Polymyxins bond to membrane lipids and the newly formed crystalline structure weakens the membrane until it bursts.

24.10.2022 by Carolin Arndt Foppa

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Enlarged view: Graphical abstract — Model of the mechanism of action of polymyxins (graphical abstract). 1 Polymyxins initially localise on the outer membrane of Gram-negative bacteria through electrostatic interactions with lipopolysaccharides. 2 On the membrane, polymyxins form hexagonal crystalline structures that increase the membrane surface area, decrease the membrane bilayer height, and stiffen the membrane. The altered mechanical properties of the outer membrane lead to (3a) the formation of membrane bulging protrusions and (3b) membrane rupture, content leak, which allows progression to the inner membrane and subsequent bacterial death. (From Manioglu et al., *Nature Communications*, https://doi.org/10.1038/s41467-022-33838-0)

Find original publication:

Manioglu, S, S M Modaresi, N Ritzmann, J Thoma, S A Overall, A Harms, G Pert, A Luther, A B Barnes, D Obrecht, D J Müller, and S Hiller (2022) external pageAntibiotic polymyxin arranges lipopolysaccharide into crystalline structures to solidify the bacterial membrane. Nature Communications, 13 (6195), https://doi.org/10.1038/s41467-022-33838-0

Commentary on this article:

Paiva, T O, A Viljoen, and Y F Dufrêne (2022) Sexternal pageeeing the unseen: High-resolution AFM imaging captures antibiotic action in bacterial membranes. Nature Communications, 13 (6196), https://doi.org/10.1038/s41467-022-33839-z

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