Abstract
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. Critical to its function, the highly asymmetric lipid distribution between the inner and outer bilayer leaflets of the OM, adds an extra level of complexity to the study of this crucial defence barrier. Here we review 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. The differential sensitivity of neutrons towards hydrogen and deuterium makes them a unique probe to study the structure and behaviour of asymmetric membranes. Molecular-level understanding of the interactions between antimicrobials and the Gram-negative OM provides valuable insights that can aid drug development and broaden our knowledge of this critically important biological barrier.
Highlights
Within the list of the highest-priority drug resistant pathogens highlighted by a recent WHO report, Gram-negative bacteria outnumber Gram-positives seven to two, with the top three critical-priority organisms all belonging to the Gram-negative class [1]
The key reason behind the success of Gram-negative bacteria in avoiding the noxious effects of antibiotics lies in the structure of their cell envelope [2]
The distinctive double membrane architecture which surrounds Gram-negative organisms comprises the canonical plasma membrane enclosed by an additional outer membrane (OM), with a thin layer of peptidoglycan sandwiched in the periplasmic space in between them (Figure 1a)
Summary
Studying the surfaces of bacteria using neutron scattering: finding new openings for antibiotics. 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. 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. The differential sensitivity of neutrons towards hydrogen and deuterium makes them a unique probe to study the structure and behaviour of asymmetric membranes. Molecular-level understanding of the interactions between antimicrobials and the Gramnegative OM provides valuable insights that can aid drug development and broaden our knowledge of this critically important biological barrier
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