Establishing Galleria mellonella, the larvae of the greater wax moth, as a model for mycobacterial infections to assess existing and novel treatments

Abstract

Galleria mellonella, the larvae of the greater wax moth, are cheap, practical and
readily-available organisms which can be utilised for a comprehensive range of
experimental protocols. They are valuable in vivo intermediaries between in vitro
studies and models which require greater investments of time, equipment, and ethical
approval. Larvae exhibit cellular and humoral immune responses with structural and
functional similarities to mammals. They are ideal for high-throughput screens of
pathogens, antimicrobials, toxicity tests, and novel treatments.
In this thesis, G. mellonella was used with a range of Mycobacterium species and
strains. Mycobacteria represent a unique challenge as they are intrinsically resistant to
antibiotics, “hide” from immune responses, and interact directly with immune cells.
Mycobacterium tuberculosis, the causative agent in tuberculosis, has infected billions of
humans and is notoriously difficult to study due to its slow generation time and ability
to infect immunocompetent humans. Hence, using related Mycobacterial species allows
assessment of this genus with minimal risk and inconvenience. Using these bacteria in
tandem with a simple, easily used in vivo model allows for a greater range of
experiments in a standard laboratory.

When this thesis commenced, Mycobacteria had not been used with a Galleria
model in the modern era, Therefore, M. fortuitum, M. marinum and M. aurum were
assessed with G. mellonella and confirmed to cause larval death. Various anti-
Mycobacterials were assessed, alongside uncommon treatment combinations such as β lactams and efflux pump inhibitors. The immune response to infection and treatment
was evaluated – the number of immune cells, their ability to phagocytose Mycobacteria,
and the formation of melanised nodules were all affected by infection and the
antibiotics used to treat them.

This work demonstrates the suitability of G. mellonella as a model for Mycobacterial
infections and indicates how they may be used in further research efforts.

Date of Award	1 Dec 2020
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Peter John Coote (Supervisor)