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

Asai, Masanori; Li, Yanwen; Spiropoulos, John; Cooley, William; Everest, David J.; Kendall, Sharon; Martín, Carlos; Robertson, Brian D.; Langford, Paul R.; Newton, Sandra M.

Abstract

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. Infection of larvae of the insect Galleria mellonella (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, and to determine comparative virulence of MTB isogenic mutants.

Importance: Conventional infection models (e.g., mice), are time consuming, expensive, and require
ethical approval hindering tuberculosis research. Here we demonstrate that Galleria mellonella
(greater wax moth) larvae, provide a low cost, rapid and ethically more acceptable model for
tuberculosis research. This is the first study to infect G. mellonella with fully virulent Mycobacterium
tuberculosis. Comparative infection studies with other mycobacteria and attenuated mutants of M.
tuberculosis indicated that G. mellonella is capable of distinguishing changes in mycobacterial
virulence. We also demonstrate Gm infection with MTB mimics a key aspect of disease (the
granuloma); and can be used for drug testing. Our findings indicate that G. mellonella will be a
practical, valuable and advantageous additional model to be used alongside existing models to
advance tuberculosis research.

Citation

Asai, M., Li, Y., Spiropoulos, J., Cooley, W., Everest, D. J., Kendall, S., Martín, C., Robertson, B. D., Langford, P. R., & Newton, S. M. (2022). Galleria mellonella as an infection model for the virulent Mycobacterium tuberculosis H37Rv. Virulence, https://doi.org/10.1080/21505594.2022.2119657

• Journal Article Type: Article
• Acceptance Date: Aug 27, 2022
• Publication Date: Sep 11, 2022
• Deposit Date: Apr 23, 2022
• Publicly Available Date: Sep 27, 2022
• Print ISSN: 2150-5594
• Electronic ISSN: 2150-5608
• Publisher: Taylor & Francis Open Access
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1080/21505594.2022.2119657
• Additional Information: RVC not the lead institution