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The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

Lydia Powell Orcid Logo, Manon F. Pritchard, Lydia C. Powell, Saira Khan, Peter C. Griffiths, Omar T. Mansour, Ralf Schweins, Konrad Beck, Niklaas J. Buurma, Christopher E. Dempsey, Chris J. Wright, Philip D. Rye, Katja E. Hill, David W. Thomas, Elaine L. Ferguson, Christopher Wright Orcid Logo

Scientific Reports (Nature group), Volume: 7, Start page: 44731

Swansea University Authors: Lydia Powell Orcid Logo, Christopher Wright Orcid Logo

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DOI (Published version): 10.1038/srep44731

Abstract

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial c...

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Published in: Scientific Reports (Nature group)
ISSN: 2045-2322
Published: 2017
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URI: https://cronfa.swan.ac.uk/Record/cronfa32518
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OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.</abstract><type>Journal Article</type><journal>Scientific Reports (Nature group)</journal><volume>7</volume><paginationStart>44731</paginationStart><publisher/><issnElectronic>2045-2322</issnElectronic><keywords>Antimicrobials, Biophysics, Medical research</keywords><publishedDay>31</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2017</publishedYear><publishedDate>2017-03-31</publishedDate><doi>10.1038/srep44731</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2017-07-07T11:36:55.5689635</lastEdited><Created>2017-03-21T16:18:39.8570687</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Engineering and Applied Sciences - Biomedical Engineering</level></path><authors><author><firstname>Lydia</firstname><surname>Powell</surname><orcid>0000-0002-8641-0160</orcid><order>1</order></author><author><firstname>Manon F.</firstname><surname>Pritchard</surname><order>2</order></author><author><firstname>Lydia C.</firstname><surname>Powell</surname><order>3</order></author><author><firstname>Saira</firstname><surname>Khan</surname><order>4</order></author><author><firstname>Peter C.</firstname><surname>Griffiths</surname><order>5</order></author><author><firstname>Omar T.</firstname><surname>Mansour</surname><order>6</order></author><author><firstname>Ralf</firstname><surname>Schweins</surname><order>7</order></author><author><firstname>Konrad</firstname><surname>Beck</surname><order>8</order></author><author><firstname>Niklaas J.</firstname><surname>Buurma</surname><order>9</order></author><author><firstname>Christopher E.</firstname><surname>Dempsey</surname><order>10</order></author><author><firstname>Chris J.</firstname><surname>Wright</surname><order>11</order></author><author><firstname>Philip D.</firstname><surname>Rye</surname><order>12</order></author><author><firstname>Katja E.</firstname><surname>Hill</surname><order>13</order></author><author><firstname>David W.</firstname><surname>Thomas</surname><order>14</order></author><author><firstname>Elaine L.</firstname><surname>Ferguson</surname><order>15</order></author><author><firstname>Christopher</firstname><surname>Wright</surname><orcid>0000-0003-2375-8159</orcid><order>16</order></author></authors><documents><document><filename>0032518-05042017152310.pdf</filename><originalFilename>pritchard2017.pdf</originalFilename><uploaded>2017-04-05T15:23:10.4270000</uploaded><type>Output</type><contentLength>1098106</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><embargoDate>2017-04-05T00:00:00.0000000</embargoDate><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2017-07-07T11:36:55.5689635 v2 32518 2017-03-21 The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 235e125ac3463e2ee7fc98604bf879ce 0000-0003-2375-8159 Christopher Wright Christopher Wright true false 2017-03-21 BMS Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification. Journal Article Scientific Reports (Nature group) 7 44731 2045-2322 Antimicrobials, Biophysics, Medical research 31 3 2017 2017-03-31 10.1038/srep44731 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2017-07-07T11:36:55.5689635 2017-03-21T16:18:39.8570687 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Lydia Powell 0000-0002-8641-0160 1 Manon F. Pritchard 2 Lydia C. Powell 3 Saira Khan 4 Peter C. Griffiths 5 Omar T. Mansour 6 Ralf Schweins 7 Konrad Beck 8 Niklaas J. Buurma 9 Christopher E. Dempsey 10 Chris J. Wright 11 Philip D. Rye 12 Katja E. Hill 13 David W. Thomas 14 Elaine L. Ferguson 15 Christopher Wright 0000-0003-2375-8159 16 0032518-05042017152310.pdf pritchard2017.pdf 2017-04-05T15:23:10.4270000 Output 1098106 application/pdf Version of Record true 2017-04-05T00:00:00.0000000 true eng
title The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
spellingShingle The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
Lydia Powell
Christopher Wright
title_short The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
title_full The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
title_fullStr The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
title_full_unstemmed The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
title_sort The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
author_id_str_mv 0e7e702952672bcbfdfd4974199202fb
235e125ac3463e2ee7fc98604bf879ce
author_id_fullname_str_mv 0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
235e125ac3463e2ee7fc98604bf879ce_***_Christopher Wright
author Lydia Powell
Christopher Wright
author2 Lydia Powell
Manon F. Pritchard
Lydia C. Powell
Saira Khan
Peter C. Griffiths
Omar T. Mansour
Ralf Schweins
Konrad Beck
Niklaas J. Buurma
Christopher E. Dempsey
Chris J. Wright
Philip D. Rye
Katja E. Hill
David W. Thomas
Elaine L. Ferguson
Christopher Wright
format Journal article
container_title Scientific Reports (Nature group)
container_volume 7
container_start_page 44731
publishDate 2017
institution Swansea University
issn 2045-2322
doi_str_mv 10.1038/srep44731
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
document_store_str 1
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description Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.
published_date 2017-03-31T03:39:51Z
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