No Cover Image

Journal article 78 views 11 downloads

Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane

Manon F. Pritchard Orcid Logo, Wenya Xue Orcid Logo, Jingxiang Wu Orcid Logo, Francesca Boardman Orcid Logo, Mei Li Orcid Logo, Yuqing Zhou Orcid Logo, Saira Khan Orcid Logo, Lydia Powell Orcid Logo, Joana Stokniene Orcid Logo, Josh Davies-Jones Orcid Logo, Philip R. Davies Orcid Logo, Niklaas J. Buurma Orcid Logo, Georgina E. Menzies Orcid Logo, Owen B. Spiller Orcid Logo, Timothy R. Walsh Orcid Logo, Paul Reddell Orcid Logo, Katja E. Hill Orcid Logo, David W. Thomas Orcid Logo

mBio, Start page: e02314-25

Swansea University Author: Lydia Powell Orcid Logo

  • 71217.VOR.pdf

    PDF | Version of Record

    Copyright © 2025 Pritchard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

    Download (4.7MB)

Check full text

DOI (Published version): 10.1128/mbio.02314-25

Abstract

The unrestricted use of colistin in animal husbandry has led to the emergence of mobile plasmid-borne colistin resistance (mcr). The antimicrobial epoxytigliane, EBC-1013, has been shown to be effective in the topical treatment of biofilm-mediated infections in vivo . Hypothesizing that EBC-1013 int...

Full description

Published in: mBio
ISSN: 2150-7511
Published: American Society for Microbiology 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa71217
first_indexed 2026-01-08T15:08:18Z
last_indexed 2026-01-09T05:32:19Z
id cronfa71217
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2026-01-08T15:13:48.7992371</datestamp><bib-version>v2</bib-version><id>71217</id><entry>2026-01-08</entry><title>Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane</title><swanseaauthors><author><sid>0e7e702952672bcbfdfd4974199202fb</sid><ORCID>0000-0002-8641-0160</ORCID><firstname>Lydia</firstname><surname>Powell</surname><name>Lydia Powell</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2026-01-08</date><deptcode>MEDS</deptcode><abstract>The unrestricted use of colistin in animal husbandry has led to the emergence of mobile plasmid-borne colistin resistance (mcr). The antimicrobial epoxytigliane, EBC-1013, has been shown to be effective in the topical treatment of biofilm-mediated infections in vivo . Hypothesizing that EBC-1013 interacts with the modified bacterial outer membrane of colistin-resistant Escherichia coli, we investigated its ability to potentiate the activity of colistin using fractional inhibitory concentration (FIC) index determinations against environmental mcr Enterobacteriaceae. Molecular dynamics (MD) simulations were used to visualize EBC-1013 interactions with the outer membrane in silico . Modification of outer membrane surface chemistry and adhesion properties was characterized using X-ray photoelectron spectroscopy (XPS) and hydrophobicity and bacterial membrane permeability assays. Anti-biofilm activity was quantified using confocal laser scanning microscopy (CLSM). Checkerboard assays revealed synergistic effects of EBC-1013 with colistin (FIC &#x2264; 0.5) in 6/9 strains. MD simulations demonstrated weak EBC-1013 interactions with colistin and the outer membrane. XPS suggested modification of the outer membrane in both colistin-sensitive and colistin-resistant E. coli, as well as the interaction of colistin and EBC-1013 with the phosphoethanolamine (pEtN)-substituted mcr lipid moiety. EBC-1013 binding significantly decreased bacterial hydrophilicity and potentiated membrane permeability induced by colistin (P &lt; 0.05). In the biofilm model, potentiation was also evident, with a marked decrease in bacterial biomass in EBC-1013/colistin combined treatments (P &lt; 0.0001) for colistin-resistant E. coli . The results highlight the ability of EBC-1013 to modify the bacterial membrane of colistin-resistant E. coli and potentiate the activity of colistin in the treatment of multidrug-resistant wound bacteria. IMPORTANCE Resistance to colistin, an antibiotic of last resort for hard-to-treat infections, is on the increase. Therefore, the need to develop new antimicrobials to tackle antimicrobial resistance is of paramount importance. The epoxytiglianes represent an exciting range of molecules with a diverse range of biological effects in human and veterinary applications, including antimicrobial properties. In this study, we show how EBC-1013 interacts with the outer surface of colistin-resistant Escherichia coli cells, inducing chemical and structural changes to the cell wall, making it susceptible again to colistin treatment. This ability of EBC-1013 to enhance the activity of colistin against a range of colistin-resistant E. coli suggests that EBC-1013, alone (or as a combination therapy), has potential as a new treatment strategy to treat antibiotic-resistant bacterial wound infections and reduce antibiotic usage. This study is registered with ClinicalTrials.gov as (Australian New Zealand Clinical Trials Register: ACTRN12624000544572 ).</abstract><type>Journal Article</type><journal>mBio</journal><volume>0</volume><journalNumber/><paginationStart>e02314-25</paginationStart><paginationEnd/><publisher>American Society for Microbiology</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2150-7511</issnElectronic><keywords>antimicrobial resistance (AMR), plasmid, mcr-1, mcr-3</keywords><publishedDay>29</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-12-29</publishedDate><doi>10.1128/mbio.02314-25</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>This work was funded by the ACCELERATE East program and the European Regional Development Fund under grant number 515454 (to D.W.T. and L.C.P.). This work also received support from QBiotics Group Ltd. (to L.C.P., M.F.P., K.E.H., and D.W.T.) and through a Ph.D. studentship for W.X.</funders><projectreference/><lastEdited>2026-01-08T15:13:48.7992371</lastEdited><Created>2026-01-08T14:58:42.0902404</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Manon F.</firstname><surname>Pritchard</surname><orcid>0000-0002-5135-4744</orcid><order>1</order></author><author><firstname>Wenya</firstname><surname>Xue</surname><orcid>0000-0002-6842-1288</orcid><order>2</order></author><author><firstname>Jingxiang</firstname><surname>Wu</surname><orcid>0009-0008-8907-7368</orcid><order>3</order></author><author><firstname>Francesca</firstname><surname>Boardman</surname><orcid>0009-0005-9917-061X</orcid><order>4</order></author><author><firstname>Mei</firstname><surname>Li</surname><orcid>0009-0008-6013-9211</orcid><order>5</order></author><author><firstname>Yuqing</firstname><surname>Zhou</surname><orcid>0009-0003-3613-4027</orcid><order>6</order></author><author><firstname>Saira</firstname><surname>Khan</surname><orcid>0000-0002-3284-3198</orcid><order>7</order></author><author><firstname>Lydia</firstname><surname>Powell</surname><orcid>0000-0002-8641-0160</orcid><order>8</order></author><author><firstname>Joana</firstname><surname>Stokniene</surname><orcid>0000-0002-8836-4209</orcid><order>9</order></author><author><firstname>Josh</firstname><surname>Davies-Jones</surname><orcid>0000-0002-9967-5467</orcid><order>10</order></author><author><firstname>Philip R.</firstname><surname>Davies</surname><orcid>0000-0003-4394-766X</orcid><order>11</order></author><author><firstname>Niklaas J.</firstname><surname>Buurma</surname><orcid>0000-0003-0260-5057</orcid><order>12</order></author><author><firstname>Georgina E.</firstname><surname>Menzies</surname><orcid>0000-0002-6600-6507</orcid><order>13</order></author><author><firstname>Owen B.</firstname><surname>Spiller</surname><orcid>0000-0002-9117-6911</orcid><order>14</order></author><author><firstname>Timothy R.</firstname><surname>Walsh</surname><orcid>0000-0003-4315-4096</orcid><order>15</order></author><author><firstname>Paul</firstname><surname>Reddell</surname><orcid>0000-0002-0993-8957</orcid><order>16</order></author><author><firstname>Katja E.</firstname><surname>Hill</surname><orcid>0000-0002-8590-0117</orcid><order>17</order></author><author><firstname>David W.</firstname><surname>Thomas</surname><orcid>0000-0001-7319-5820</orcid><order>18</order></author></authors><documents><document><filename>71217__35931__c1c3687d6645449abac2371b8162e605.pdf</filename><originalFilename>71217.VOR.pdf</originalFilename><uploaded>2026-01-08T15:06:41.4818613</uploaded><type>Output</type><contentLength>4926881</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright &#xA9; 2025 Pritchard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>https://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2026-01-08T15:13:48.7992371 v2 71217 2026-01-08 Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 2026-01-08 MEDS The unrestricted use of colistin in animal husbandry has led to the emergence of mobile plasmid-borne colistin resistance (mcr). The antimicrobial epoxytigliane, EBC-1013, has been shown to be effective in the topical treatment of biofilm-mediated infections in vivo . Hypothesizing that EBC-1013 interacts with the modified bacterial outer membrane of colistin-resistant Escherichia coli, we investigated its ability to potentiate the activity of colistin using fractional inhibitory concentration (FIC) index determinations against environmental mcr Enterobacteriaceae. Molecular dynamics (MD) simulations were used to visualize EBC-1013 interactions with the outer membrane in silico . Modification of outer membrane surface chemistry and adhesion properties was characterized using X-ray photoelectron spectroscopy (XPS) and hydrophobicity and bacterial membrane permeability assays. Anti-biofilm activity was quantified using confocal laser scanning microscopy (CLSM). Checkerboard assays revealed synergistic effects of EBC-1013 with colistin (FIC ≤ 0.5) in 6/9 strains. MD simulations demonstrated weak EBC-1013 interactions with colistin and the outer membrane. XPS suggested modification of the outer membrane in both colistin-sensitive and colistin-resistant E. coli, as well as the interaction of colistin and EBC-1013 with the phosphoethanolamine (pEtN)-substituted mcr lipid moiety. EBC-1013 binding significantly decreased bacterial hydrophilicity and potentiated membrane permeability induced by colistin (P < 0.05). In the biofilm model, potentiation was also evident, with a marked decrease in bacterial biomass in EBC-1013/colistin combined treatments (P < 0.0001) for colistin-resistant E. coli . The results highlight the ability of EBC-1013 to modify the bacterial membrane of colistin-resistant E. coli and potentiate the activity of colistin in the treatment of multidrug-resistant wound bacteria. IMPORTANCE Resistance to colistin, an antibiotic of last resort for hard-to-treat infections, is on the increase. Therefore, the need to develop new antimicrobials to tackle antimicrobial resistance is of paramount importance. The epoxytiglianes represent an exciting range of molecules with a diverse range of biological effects in human and veterinary applications, including antimicrobial properties. In this study, we show how EBC-1013 interacts with the outer surface of colistin-resistant Escherichia coli cells, inducing chemical and structural changes to the cell wall, making it susceptible again to colistin treatment. This ability of EBC-1013 to enhance the activity of colistin against a range of colistin-resistant E. coli suggests that EBC-1013, alone (or as a combination therapy), has potential as a new treatment strategy to treat antibiotic-resistant bacterial wound infections and reduce antibiotic usage. This study is registered with ClinicalTrials.gov as (Australian New Zealand Clinical Trials Register: ACTRN12624000544572 ). Journal Article mBio 0 e02314-25 American Society for Microbiology 2150-7511 antimicrobial resistance (AMR), plasmid, mcr-1, mcr-3 29 12 2025 2025-12-29 10.1128/mbio.02314-25 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee This work was funded by the ACCELERATE East program and the European Regional Development Fund under grant number 515454 (to D.W.T. and L.C.P.). This work also received support from QBiotics Group Ltd. (to L.C.P., M.F.P., K.E.H., and D.W.T.) and through a Ph.D. studentship for W.X. 2026-01-08T15:13:48.7992371 2026-01-08T14:58:42.0902404 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Manon F. Pritchard 0000-0002-5135-4744 1 Wenya Xue 0000-0002-6842-1288 2 Jingxiang Wu 0009-0008-8907-7368 3 Francesca Boardman 0009-0005-9917-061X 4 Mei Li 0009-0008-6013-9211 5 Yuqing Zhou 0009-0003-3613-4027 6 Saira Khan 0000-0002-3284-3198 7 Lydia Powell 0000-0002-8641-0160 8 Joana Stokniene 0000-0002-8836-4209 9 Josh Davies-Jones 0000-0002-9967-5467 10 Philip R. Davies 0000-0003-4394-766X 11 Niklaas J. Buurma 0000-0003-0260-5057 12 Georgina E. Menzies 0000-0002-6600-6507 13 Owen B. Spiller 0000-0002-9117-6911 14 Timothy R. Walsh 0000-0003-4315-4096 15 Paul Reddell 0000-0002-0993-8957 16 Katja E. Hill 0000-0002-8590-0117 17 David W. Thomas 0000-0001-7319-5820 18 71217__35931__c1c3687d6645449abac2371b8162e605.pdf 71217.VOR.pdf 2026-01-08T15:06:41.4818613 Output 4926881 application/pdf Version of Record true Copyright © 2025 Pritchard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. true eng https://creativecommons.org/licenses/by/4.0/
title Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
spellingShingle Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
Lydia Powell
title_short Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
title_full Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
title_fullStr Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
title_full_unstemmed Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
title_sort Epoxytiglianes potentiate the activity of colistin against resistant Escherichia coli via modification of the bacterial cell membrane
author_id_str_mv 0e7e702952672bcbfdfd4974199202fb
author_id_fullname_str_mv 0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
author Lydia Powell
author2 Manon F. Pritchard
Wenya Xue
Jingxiang Wu
Francesca Boardman
Mei Li
Yuqing Zhou
Saira Khan
Lydia Powell
Joana Stokniene
Josh Davies-Jones
Philip R. Davies
Niklaas J. Buurma
Georgina E. Menzies
Owen B. Spiller
Timothy R. Walsh
Paul Reddell
Katja E. Hill
David W. Thomas
format Journal article
container_title mBio
container_volume 0
container_start_page e02314-25
publishDate 2025
institution Swansea University
issn 2150-7511
doi_str_mv 10.1128/mbio.02314-25
publisher American Society for Microbiology
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description The unrestricted use of colistin in animal husbandry has led to the emergence of mobile plasmid-borne colistin resistance (mcr). The antimicrobial epoxytigliane, EBC-1013, has been shown to be effective in the topical treatment of biofilm-mediated infections in vivo . Hypothesizing that EBC-1013 interacts with the modified bacterial outer membrane of colistin-resistant Escherichia coli, we investigated its ability to potentiate the activity of colistin using fractional inhibitory concentration (FIC) index determinations against environmental mcr Enterobacteriaceae. Molecular dynamics (MD) simulations were used to visualize EBC-1013 interactions with the outer membrane in silico . Modification of outer membrane surface chemistry and adhesion properties was characterized using X-ray photoelectron spectroscopy (XPS) and hydrophobicity and bacterial membrane permeability assays. Anti-biofilm activity was quantified using confocal laser scanning microscopy (CLSM). Checkerboard assays revealed synergistic effects of EBC-1013 with colistin (FIC ≤ 0.5) in 6/9 strains. MD simulations demonstrated weak EBC-1013 interactions with colistin and the outer membrane. XPS suggested modification of the outer membrane in both colistin-sensitive and colistin-resistant E. coli, as well as the interaction of colistin and EBC-1013 with the phosphoethanolamine (pEtN)-substituted mcr lipid moiety. EBC-1013 binding significantly decreased bacterial hydrophilicity and potentiated membrane permeability induced by colistin (P < 0.05). In the biofilm model, potentiation was also evident, with a marked decrease in bacterial biomass in EBC-1013/colistin combined treatments (P < 0.0001) for colistin-resistant E. coli . The results highlight the ability of EBC-1013 to modify the bacterial membrane of colistin-resistant E. coli and potentiate the activity of colistin in the treatment of multidrug-resistant wound bacteria. IMPORTANCE Resistance to colistin, an antibiotic of last resort for hard-to-treat infections, is on the increase. Therefore, the need to develop new antimicrobials to tackle antimicrobial resistance is of paramount importance. The epoxytiglianes represent an exciting range of molecules with a diverse range of biological effects in human and veterinary applications, including antimicrobial properties. In this study, we show how EBC-1013 interacts with the outer surface of colistin-resistant Escherichia coli cells, inducing chemical and structural changes to the cell wall, making it susceptible again to colistin treatment. This ability of EBC-1013 to enhance the activity of colistin against a range of colistin-resistant E. coli suggests that EBC-1013, alone (or as a combination therapy), has potential as a new treatment strategy to treat antibiotic-resistant bacterial wound infections and reduce antibiotic usage. This study is registered with ClinicalTrials.gov as (Australian New Zealand Clinical Trials Register: ACTRN12624000544572 ).
published_date 2025-12-29T05:33:31Z
_version_ 1856805810466717696
score 11.096047

Similar Items