High-resolution NMR studies of antibiotics in cellular membranes

João Medeiros-Silva, Shehrazade Jekhmane, Alessandra Lucini Paioni, Katarzyna Gawarecka, Marc Baldus, Ewa Swiezewska, Eefjan Breukink () and Markus Weingarth ()
Additional contact information
João Medeiros-Silva: Utrecht University
Shehrazade Jekhmane: Utrecht University
Alessandra Lucini Paioni: Utrecht University
Katarzyna Gawarecka: Polish Academy of Sciences
Marc Baldus: Utrecht University
Ewa Swiezewska: Polish Academy of Sciences
Eefjan Breukink: Utrecht University
Markus Weingarth: Utrecht University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract The alarming rise of antimicrobial resistance requires antibiotics with unexploited mechanisms. Ideal templates could be antibiotics that target the peptidoglycan precursor lipid II, known as the bacterial Achilles heel, at an irreplaceable pyrophosphate group. Such antibiotics would kill multidrug-resistant pathogens at nanomolecular concentrations without causing antimicrobial resistance. However, due to the challenge of studying small membrane-embedded drug–receptor complexes in native conditions, the structural correlates of the pharmaceutically relevant binding modes are unknown. Here, using advanced highly sensitive solid-state NMR setups, we present a high-resolution approach to study lipid II-binding antibiotics directly in cell membranes. On the example of nisin, the preeminent lantibiotic, we show that the native antibiotic-binding mode strongly differs from previously published structures, and we demonstrate that functional hotspots correspond to plastic drug domains that are critical for the cellular adaptability of nisin. Thereby, our approach provides a foundation for an improved understanding of powerful antibiotics.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06314-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06314-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06314-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().