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BioSAXS Measurements Reveal That Two Antimicrobial Peptides Induce Similar Molecular Changes in Gram-Negative and Gram-Positive Bacteria.

von Gundlach, A; Ashby, MP; Gani, J; Lopez-Perez, PM; Cookson, AR; Ann Huws, S; Rumancev, C; Garamus, VM; Mikut, R; Rosenhahn, A; et al. von Gundlach, A; Ashby, MP; Gani, J; Lopez-Perez, PM; Cookson, AR; Ann Huws, S; Rumancev, C; Garamus, VM; Mikut, R; Rosenhahn, A; Hilpert, K (2019) BioSAXS Measurements Reveal That Two Antimicrobial Peptides Induce Similar Molecular Changes in Gram-Negative and Gram-Positive Bacteria. Front Pharmacol, 10. p. 1127. ISSN 1663-9812 https://doi.org/10.3389/fphar.2019.01127
SGUL Authors: Hilpert, Kai

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Abstract

Two highly active short broad-spectrum AMPs (14D and 69D) with unknown mode of action have been investigated in regards to their effect against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA). Minimal inhibitory concentration (MIC) measurements using a cell density of 108 cfu/ml resulted in values between 16 and 32 µg/ml. Time-kill experiments using 108 cfu/ml revealed complete killing, except for 69D in combination with MRSA, where bacterial load was reduced a million times. Small-angle X-ray scattering of biological samples (BioSAXS) at 108 cfu/ml was applied to investigate the ultrastructural changes in E. coli and MRSA in response to these two broad-spectrum AMPs. In addition, electron microscopy (EM) was performed to visualize the treated and non-treated bacteria. As expected, the scattering curves generated using BioSAXS show the ultrastructure of the Gram-positive and Gram-negative bacteria to be very different (BioSAXS is not susceptible to the outer shape). After treatment with either peptide, the scattering curves of E. coli and MRSA cells are much more alike. Whereas in EM, it is notoriously difficult to observe changes for spherical Gram-positives; the BioSAXS results are superior and reveal strongly similar effects for both peptides induced in Gram-positive as well as Gram-negative bacteria. Given the high-throughput possibility and robust statistics, BioSAXS can support and speed up mode of action research in AMPs and other antimicrobial compounds, making a contribution toward the development of urgently needed drugs against resistant bacteria.

Item Type: Article
Additional Information: Copyright © 2019 von Gundlach, Ashby, Gani, Lopez-Perez, Cookson, Ann Huws, Rumancev, Garamus, Mikut, Rosenhahn and Hilpert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: E. coli, MRSA, SAXS, antimicrobial peptide, electron microscopy, mode of action, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Front Pharmacol
ISSN: 1663-9812
Language: eng
Dates:
DateEvent
26 September 2019Published
30 August 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 31616307
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111296
Publisher's version: https://doi.org/10.3389/fphar.2019.01127

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