Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for mor...

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Main Authors: Masanori Asai, Yanwen Li, John Spiropoulos, William Cooley, David J. Everest, Sharon L. Kendall, Carlos Martín, Brian D. Robertson, Paul R. Langford, Sandra M. Newton
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Virulence
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2022.2119657
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author Masanori Asai
Yanwen Li
John Spiropoulos
William Cooley
David J. Everest
Sharon L. Kendall
Carlos Martín
Brian D. Robertson
Paul R. Langford
Sandra M. Newton
author_facet Masanori Asai
Yanwen Li
John Spiropoulos
William Cooley
David J. Everest
Sharon L. Kendall
Carlos Martín
Brian D. Robertson
Paul R. Langford
Sandra M. Newton
author_sort Masanori Asai
collection DOAJ
description Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here, we demonstrate and present a basic description of how Galleria mellonella (the greater wax moth, Gm) larvae can be used as a low cost, rapid, and ethically more acceptable model for TB research. This is the first study to infect Gm with the fully virulent MTB H37Rv, the most widely used strain in research. Infection of Gm with MTB resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated Mycobacterium bovis BCG and auxotrophic MTB strains. The Gm-MTB model can also be used for anti-TB drug screening, although CFU enumeration from Gm is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of MTB isogenic mutants can be determined in Gm. However, comparison of mutant phenotypes in Gm against conventional models must consider the limitations of innate immunity. Our findings indicate that Gm will be a practical, valuable, and advantageous additional model to be used alongside existing models to advance tuberculosis research.
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spelling doaj.art-1acc6fc7085849aaab8ffc83c650b9c22022-12-22T04:24:48ZengTaylor & Francis GroupVirulence2150-55942150-56082022-12-011311543155710.1080/21505594.2022.2119657Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37RvMasanori Asai0Yanwen Li1John Spiropoulos2William Cooley3David J. Everest4Sharon L. Kendall5Carlos Martín6Brian D. Robertson7Paul R. Langford8Sandra M. Newton9Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, UKSection of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, UKDepartment of Pathology, Animal and Plant Health Agency, Addlestone, UKDepartment of Pathology, Animal and Plant Health Agency, Addlestone, UKDepartment of Pathology, Animal and Plant Health Agency, Addlestone, UKCentre for Emerging, Endemic and Exotic Diseases, Pathobiology and Population Sciences, Royal Veterinary College, Hartfield, UKDepartment of Microbiology, Facultad de Medicina Universidad de Zaragoza, Zaragoza, SpainMRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London, UKSection of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, UKSection of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, UKTuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here, we demonstrate and present a basic description of how Galleria mellonella (the greater wax moth, Gm) larvae can be used as a low cost, rapid, and ethically more acceptable model for TB research. This is the first study to infect Gm with the fully virulent MTB H37Rv, the most widely used strain in research. Infection of Gm with MTB resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated Mycobacterium bovis BCG and auxotrophic MTB strains. The Gm-MTB model can also be used for anti-TB drug screening, although CFU enumeration from Gm is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of MTB isogenic mutants can be determined in Gm. However, comparison of mutant phenotypes in Gm against conventional models must consider the limitations of innate immunity. Our findings indicate that Gm will be a practical, valuable, and advantageous additional model to be used alongside existing models to advance tuberculosis research.https://www.tandfonline.com/doi/10.1080/21505594.2022.2119657TuberculosisMycobacterium tuberculosisGalleria mellonellainfection modelinnate immunitymycobacteria
spellingShingle Masanori Asai
Yanwen Li
John Spiropoulos
William Cooley
David J. Everest
Sharon L. Kendall
Carlos Martín
Brian D. Robertson
Paul R. Langford
Sandra M. Newton
Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
Virulence
Tuberculosis
Mycobacterium tuberculosis
Galleria mellonella
infection model
innate immunity
mycobacteria
title Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
title_full Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
title_fullStr Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
title_full_unstemmed Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
title_short Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv
title_sort galleria mellonella as an infection model for the virulent mycobacterium tuberculosis h37rv
topic Tuberculosis
Mycobacterium tuberculosis
Galleria mellonella
infection model
innate immunity
mycobacteria
url https://www.tandfonline.com/doi/10.1080/21505594.2022.2119657
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