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The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus / PHILLIP BUTTERICK

Swansea University Author: PHILLIP BUTTERICK

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DOI (Published version): 10.23889/SUthesis.59037

Abstract

Antimicrobial resistance is a global health concern, with once treatable infections becoming resistant to current standard of care antimicrobials. The search for new antimicrobials has led Neem Biotech Ltd. to manufacture NX-AS-401 an ajoene containing compound derived from Allium sativuum, commonly...

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Published: Swansea 2021
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Jenkins, Rowena ; Wilkinson, Tom ; Evans, Gareth
URI: https://cronfa.swan.ac.uk/Record/cronfa59037
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first_indexed 2021-12-21T17:38:22Z
last_indexed 2021-12-22T04:26:40Z
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2021-12-21T18:03:12.9817234</datestamp><bib-version>v2</bib-version><id>59037</id><entry>2021-12-21</entry><title>The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus</title><swanseaauthors><author><sid>612efcca706d3f54f4bac65a636d89d6</sid><firstname>PHILLIP</firstname><surname>BUTTERICK</surname><name>PHILLIP BUTTERICK</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2021-12-21</date><abstract>Antimicrobial resistance is a global health concern, with once treatable infections becoming resistant to current standard of care antimicrobials. The search for new antimicrobials has led Neem Biotech Ltd. to manufacture NX-AS-401 an ajoene containing compound derived from Allium sativuum, commonly known as garlic. The research contained within this thesis aimed to identify the effects of NX-AS-401 on Methicillin Resistant Staphylococcus aureus (MRSA), one of the most well documented and commonly isolated antimicrobial resistant bacterial pathogens. A multi-stage approach was utilised, identifying how NX-AS-401 affects planktonic growth, biofilm development and virulence factor production. In Chapters 3 and 4 initial comparison between different NX-AS-401 formulations was performed in determined that ajoene content did not alter the antimicrobial effect of NX-AS-401. EUCAST broth microdilution compared NX-AS-401 to current standard of care antibiotic and determined effective inhibitory and bactericidal concentrations as 128 &#xB5;g/ml and 2048 &#xB5;g/ml respectively. When NX-AS-401 was used in combination with various antibiotic classes a synergistic effect was identified and the inhibitory concentrations of both agents were reduced. The primary focus on Chapter 5 was how NX-AS-401 affected S. aureus biofilm formation. NX-AS-401 concentrations of 32 &#xB5;g/ml inhibited biofilm formation and a concentration of 512 &#xB5;g/ml caused disruption of pre-established biofilms. These effects were confirmed using scanning electron microscopy and confocal microscopy with live/dead staining. In gene expression studies it was determined that the effects of NX-AS-401 on S. aureus biofilms were strain dependent and a target gene was not identified. Chapter 6 demonstrated that NX-AS-401 did not alter the production of Staphylococcus aureus exo-enzyme production in vitro during phenotypic studies. In Galleria mellonella low NX-AS-401 concentrations assisted in the recovery from S. aureus in a strain dependent manner, however, high concentrations caused increased Galleria mellonella fatality. NX-AS-401 altered the ability of S. aureus cells to invade human epithelial cells but did not prevent adhesion of S. aureus to the cells. NX-AS-401 has multiple effects on S. aureus with the ability to affect both planktonic cells and biofilm structure showing promise as an antimicrobial. Its main effects are growth inhibition and biofilm disruption rather than causing bacterial cell death. These attributes and the synergistic effects between NX-AS-401 and multiple antibiotic classes, indicate NX-AS-401 has potential as a strong antimicrobial adjuvant.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords>Microbiology, Bacteriology, Antibiotic Resistance, Natural compound, Garlic, Ajoene</keywords><publishedDay>21</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-12-21</publishedDate><doi>10.23889/SUthesis.59037</doi><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Jenkins, Rowena ; Wilkinson, Tom ; Evans, Gareth</supervisor><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><degreesponsorsfunders>KESS 2</degreesponsorsfunders><apcterm/><lastEdited>2021-12-21T18:03:12.9817234</lastEdited><Created>2021-12-21T17:24:44.5901004</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>PHILLIP</firstname><surname>BUTTERICK</surname><order>1</order></author></authors><documents><document><filename>Under embargo</filename><originalFilename>Under embargo</originalFilename><uploaded>2021-12-21T17:45:53.5528166</uploaded><type>Output</type><contentLength>6210430</contentLength><contentType>application/pdf</contentType><version>E-Thesis &#x2013; open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2023-12-21T00:00:00.0000000</embargoDate><documentNotes>Copyright: The author, Phillip Butterick, 2021.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2021-12-21T18:03:12.9817234 v2 59037 2021-12-21 The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus 612efcca706d3f54f4bac65a636d89d6 PHILLIP BUTTERICK PHILLIP BUTTERICK true false 2021-12-21 Antimicrobial resistance is a global health concern, with once treatable infections becoming resistant to current standard of care antimicrobials. The search for new antimicrobials has led Neem Biotech Ltd. to manufacture NX-AS-401 an ajoene containing compound derived from Allium sativuum, commonly known as garlic. The research contained within this thesis aimed to identify the effects of NX-AS-401 on Methicillin Resistant Staphylococcus aureus (MRSA), one of the most well documented and commonly isolated antimicrobial resistant bacterial pathogens. A multi-stage approach was utilised, identifying how NX-AS-401 affects planktonic growth, biofilm development and virulence factor production. In Chapters 3 and 4 initial comparison between different NX-AS-401 formulations was performed in determined that ajoene content did not alter the antimicrobial effect of NX-AS-401. EUCAST broth microdilution compared NX-AS-401 to current standard of care antibiotic and determined effective inhibitory and bactericidal concentrations as 128 µg/ml and 2048 µg/ml respectively. When NX-AS-401 was used in combination with various antibiotic classes a synergistic effect was identified and the inhibitory concentrations of both agents were reduced. The primary focus on Chapter 5 was how NX-AS-401 affected S. aureus biofilm formation. NX-AS-401 concentrations of 32 µg/ml inhibited biofilm formation and a concentration of 512 µg/ml caused disruption of pre-established biofilms. These effects were confirmed using scanning electron microscopy and confocal microscopy with live/dead staining. In gene expression studies it was determined that the effects of NX-AS-401 on S. aureus biofilms were strain dependent and a target gene was not identified. Chapter 6 demonstrated that NX-AS-401 did not alter the production of Staphylococcus aureus exo-enzyme production in vitro during phenotypic studies. In Galleria mellonella low NX-AS-401 concentrations assisted in the recovery from S. aureus in a strain dependent manner, however, high concentrations caused increased Galleria mellonella fatality. NX-AS-401 altered the ability of S. aureus cells to invade human epithelial cells but did not prevent adhesion of S. aureus to the cells. NX-AS-401 has multiple effects on S. aureus with the ability to affect both planktonic cells and biofilm structure showing promise as an antimicrobial. Its main effects are growth inhibition and biofilm disruption rather than causing bacterial cell death. These attributes and the synergistic effects between NX-AS-401 and multiple antibiotic classes, indicate NX-AS-401 has potential as a strong antimicrobial adjuvant. E-Thesis Swansea Microbiology, Bacteriology, Antibiotic Resistance, Natural compound, Garlic, Ajoene 21 12 2021 2021-12-21 10.23889/SUthesis.59037 COLLEGE NANME COLLEGE CODE Swansea University Jenkins, Rowena ; Wilkinson, Tom ; Evans, Gareth Doctoral Ph.D KESS 2 2021-12-21T18:03:12.9817234 2021-12-21T17:24:44.5901004 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine PHILLIP BUTTERICK 1 Under embargo Under embargo 2021-12-21T17:45:53.5528166 Output 6210430 application/pdf E-Thesis – open access true 2023-12-21T00:00:00.0000000 Copyright: The author, Phillip Butterick, 2021. true eng
title The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
spellingShingle The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
PHILLIP BUTTERICK
title_short The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
title_full The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
title_fullStr The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
title_full_unstemmed The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
title_sort The effects of NX-AS-401 on methicillin resistant Staphylococcus aureus
author_id_str_mv 612efcca706d3f54f4bac65a636d89d6
author_id_fullname_str_mv 612efcca706d3f54f4bac65a636d89d6_***_PHILLIP BUTTERICK
author PHILLIP BUTTERICK
author2 PHILLIP BUTTERICK
format E-Thesis
publishDate 2021
institution Swansea University
doi_str_mv 10.23889/SUthesis.59037
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 - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Antimicrobial resistance is a global health concern, with once treatable infections becoming resistant to current standard of care antimicrobials. The search for new antimicrobials has led Neem Biotech Ltd. to manufacture NX-AS-401 an ajoene containing compound derived from Allium sativuum, commonly known as garlic. The research contained within this thesis aimed to identify the effects of NX-AS-401 on Methicillin Resistant Staphylococcus aureus (MRSA), one of the most well documented and commonly isolated antimicrobial resistant bacterial pathogens. A multi-stage approach was utilised, identifying how NX-AS-401 affects planktonic growth, biofilm development and virulence factor production. In Chapters 3 and 4 initial comparison between different NX-AS-401 formulations was performed in determined that ajoene content did not alter the antimicrobial effect of NX-AS-401. EUCAST broth microdilution compared NX-AS-401 to current standard of care antibiotic and determined effective inhibitory and bactericidal concentrations as 128 µg/ml and 2048 µg/ml respectively. When NX-AS-401 was used in combination with various antibiotic classes a synergistic effect was identified and the inhibitory concentrations of both agents were reduced. The primary focus on Chapter 5 was how NX-AS-401 affected S. aureus biofilm formation. NX-AS-401 concentrations of 32 µg/ml inhibited biofilm formation and a concentration of 512 µg/ml caused disruption of pre-established biofilms. These effects were confirmed using scanning electron microscopy and confocal microscopy with live/dead staining. In gene expression studies it was determined that the effects of NX-AS-401 on S. aureus biofilms were strain dependent and a target gene was not identified. Chapter 6 demonstrated that NX-AS-401 did not alter the production of Staphylococcus aureus exo-enzyme production in vitro during phenotypic studies. In Galleria mellonella low NX-AS-401 concentrations assisted in the recovery from S. aureus in a strain dependent manner, however, high concentrations caused increased Galleria mellonella fatality. NX-AS-401 altered the ability of S. aureus cells to invade human epithelial cells but did not prevent adhesion of S. aureus to the cells. NX-AS-401 has multiple effects on S. aureus with the ability to affect both planktonic cells and biofilm structure showing promise as an antimicrobial. Its main effects are growth inhibition and biofilm disruption rather than causing bacterial cell death. These attributes and the synergistic effects between NX-AS-401 and multiple antibiotic classes, indicate NX-AS-401 has potential as a strong antimicrobial adjuvant.
published_date 2021-12-21T04:16:01Z
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score 11.01288

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