BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria

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BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria. / von Gundlach, Andreas; Ashby, Martin P.; Gani, Jurnorain; Lopez-Perez, Paula Matilde; Cookson, Alan; Huws, Sharon; Rumancev, Christoph; Garamus, Vasil M.; Mikut, Ralf; Rosenhahn, Axel; Hilpert, Kai.

In: Frontiers in Pharmacology, Vol. 10, 1127, 26.09.2019.

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Harvard

von Gundlach, A, Ashby, MP, Gani, J, Lopez-Perez, PM, Cookson, A, 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' Frontiers in Pharmacology, vol. 10, 1127. https://doi.org/10.3389/fphar.2019.01127

APA

von Gundlach, A., Ashby, M. P., Gani, J., Lopez-Perez, P. M., Cookson, A., Huws, S., ... Hilpert, K. (2019). BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria. Frontiers in Pharmacology, 10, [1127]. https://doi.org/10.3389/fphar.2019.01127

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von Gundlach, Andreas ; Ashby, Martin P. ; Gani, Jurnorain ; Lopez-Perez, Paula Matilde ; Cookson, Alan ; Huws, Sharon ; Rumancev, Christoph ; Garamus, Vasil M. ; Mikut, Ralf ; Rosenhahn, Axel ; Hilpert, Kai. / BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria. In: Frontiers in Pharmacology. 2019 ; Vol. 10.

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@article{b36389af758a4459b42f78a17edf7554,
title = "BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria",
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",
keywords = "antimicrobial peptide, mode of action, SAXS, MRSA, electron microscopy, E. coli",
author = "{von Gundlach}, Andreas and Ashby, {Martin P.} and Jurnorain Gani and Lopez-Perez, {Paula Matilde} and Alan Cookson and Sharon Huws and Christoph Rumancev and Garamus, {Vasil M.} and Ralf Mikut and Axel Rosenhahn and Kai Hilpert",
year = "2019",
month = "9",
day = "26",
doi = "10.3389/fphar.2019.01127",
language = "English",
volume = "10",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media",

}

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TY - JOUR

T1 - BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in gram-negative and gram-positive bacteria

AU - von Gundlach, Andreas

AU - Ashby, Martin P.

AU - Gani, Jurnorain

AU - Lopez-Perez, Paula Matilde

AU - Cookson, Alan

AU - Huws, Sharon

AU - Rumancev, Christoph

AU - Garamus, Vasil M.

AU - Mikut, Ralf

AU - Rosenhahn, Axel

AU - Hilpert, Kai

PY - 2019/9/26

Y1 - 2019/9/26

N2 - 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

AB - 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

KW - antimicrobial peptide

KW - mode of action

KW - SAXS

KW - MRSA

KW - electron microscopy

KW - E. coli

U2 - 10.3389/fphar.2019.01127

DO - 10.3389/fphar.2019.01127

M3 - Article

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 1127

ER -

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