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Prospecting the insect model, Galleria mellonella, for gut-related pathobiology / HELENA EMERY

Swansea University Author: HELENA EMERY

DOI (Published version): 10.23889/SUthesis.56984

Abstract

Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human...

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Published: Swansea 2020
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Coates, Christopher J. ; Butt, Tariq
URI: https://cronfa.swan.ac.uk/Record/cronfa56984
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Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host&#x2019;s capacity to recover from subacute chemical and microbial disruptors.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords>Cordyceps sinensis, Galleria mellonella, Nutraceuticals, Gastrointestinal pathology, Non-steroidal anti-inflammatory drugs (NSAID), Campylobacter jejuni, Histology, haemocytes, microbiome</keywords><publishedDay>27</publishedDay><publishedMonth>8</publishedMonth><publishedYear>2020</publishedYear><publishedDate>2020-08-27</publishedDate><doi>10.23889/SUthesis.56984</doi><url/><notes>ORCiD identifier https://orcid.org/0000-0003-1890-4254</notes><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Coates, Christopher J. ; Butt, Tariq</supervisor><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><degreesponsorsfunders>KESS 2 (supported Mr John Rolfs, The Golden Dairy Ltd.)</degreesponsorsfunders><apcterm/><lastEdited>2021-05-28T17:06:16.1083909</lastEdited><Created>2021-05-28T16:37:10.3599324</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Biosciences, Geography and Physics - Biosciences</level></path><authors><author><firstname>HELENA</firstname><surname>EMERY</surname><order>1</order></author></authors><documents><document><filename>56984__20027__8170a63e78464da4b8c8df7db4d98738.pdf</filename><originalFilename>Emery_Helena_PhD_Thesis_Final_Redacted_Signatures.pdf</originalFilename><uploaded>2021-05-28T16:54:51.8411092</uploaded><type>Output</type><contentLength>13223763</contentLength><contentType>application/pdf</contentType><version>E-Thesis &#x2013; open access</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright: The author, Helena Emery, 2020.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2021-05-28T17:06:16.1083909 v2 56984 2021-05-28 Prospecting the insect model, Galleria mellonella, for gut-related pathobiology bda5e75820cd612b39cec952914fb90a HELENA EMERY HELENA EMERY true false 2021-05-28 Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human genes and is the most widespread vertebrate model in use. Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host’s capacity to recover from subacute chemical and microbial disruptors. E-Thesis Swansea Cordyceps sinensis, Galleria mellonella, Nutraceuticals, Gastrointestinal pathology, Non-steroidal anti-inflammatory drugs (NSAID), Campylobacter jejuni, Histology, haemocytes, microbiome 27 8 2020 2020-08-27 10.23889/SUthesis.56984 ORCiD identifier https://orcid.org/0000-0003-1890-4254 COLLEGE NANME COLLEGE CODE Swansea University Coates, Christopher J. ; Butt, Tariq Doctoral Ph.D KESS 2 (supported Mr John Rolfs, The Golden Dairy Ltd.) 2021-05-28T17:06:16.1083909 2021-05-28T16:37:10.3599324 Faculty of Science and Engineering School of Biosciences, Geography and Physics - Biosciences HELENA EMERY 1 56984__20027__8170a63e78464da4b8c8df7db4d98738.pdf Emery_Helena_PhD_Thesis_Final_Redacted_Signatures.pdf 2021-05-28T16:54:51.8411092 Output 13223763 application/pdf E-Thesis – open access true Copyright: The author, Helena Emery, 2020. true eng
title Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
spellingShingle Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
HELENA EMERY
title_short Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
title_full Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
title_fullStr Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
title_full_unstemmed Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
title_sort Prospecting the insect model, Galleria mellonella, for gut-related pathobiology
author_id_str_mv bda5e75820cd612b39cec952914fb90a
author_id_fullname_str_mv bda5e75820cd612b39cec952914fb90a_***_HELENA EMERY
author HELENA EMERY
author2 HELENA EMERY
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institution Swansea University
doi_str_mv 10.23889/SUthesis.56984
college_str Faculty of Science and Engineering
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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 Biosciences, Geography and Physics - Biosciences{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Biosciences, Geography and Physics - Biosciences
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description Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human genes and is the most widespread vertebrate model in use. Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host’s capacity to recover from subacute chemical and microbial disruptors.
published_date 2020-08-27T04:12:22Z
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score 11.013148

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