Galleria mellonellainfection models for the study of bacterial diseases and for antimicrobial drug testing

Abstract

Galleria mellonella (greater wax moth or honeycomb moth) has been introduced as an alternative model to study microbial infections. G. mellonella larvae can be easily and inexpensively obtained in large numbers and are simple to use as they don't require special lab equipment. There are no ethical constraints and their short life cycle makes them ideal for large-scale studies. Although insects lack an adaptive immune response, their innate immune response shows remarkable similarities with the immune response in vertebrates.This review gives a current update of what is known about the immune system of G. mellonella and provides an extensive overview of how G. mellonella is used to study the virulence of Gram-positive and Gram-negative bacteria. In addition, the use of G. mellonella to evaluate the efficacy of antimicrobial agents and experimental phage therapy are also discussed. The review concludes with a critical assessment of the current limitatons of G. mellonella infection models.

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

“…Over 1000 articles have been published on the use of G. mellonella as a surrogate host infection model for studying the pathogenesis of micro-organisms, with more than 200 publications in 2014–2015 alone [15]. Advantages of using this insect larva include, no ethical implications, wide availability of larvae from commercial suppliers, low cost, simple housing and easy maintenance at 37°C, which also mimics the human host, large size (20–30 mm) allowing easy manipulation without the need for anaesthesia, precision injection into the haemocel through the last pro-leg, and the availability of host tissue/haemolymph for experimental analysis [11,15,19,20].…”

“…Advantages of using this insect larva include, no ethical implications, wide availability of larvae from commercial suppliers, low cost, simple housing and easy maintenance at 37°C, which also mimics the human host, large size (20–30 mm) allowing easy manipulation without the need for anaesthesia, precision injection into the haemocel through the last pro-leg, and the availability of host tissue/haemolymph for experimental analysis [11,15,19,20]. In addition, a good correlation has been established between the pathogenicity of several micro-organisms in G. mellonella with vertebrate models of infection [49].…”

“…Whilst G. mellonella larvae do not possess an adaptive immune system they do display an innate immune system similar to humans with many analogous functions including, phagocytosis of pathogens by haemocytes [17,34,52–54], a similar cell type to human macrophages and neutrophils [36]. They also produce antimicrobial peptides, complement-like proteins and reactive oxygen and nitrogen species for killing ingested pathogens, all found within the haemolymph, a biological fluid similar to mammalian blood [15,16,18]. We speculate that death of infected larvae with higher M. bovis BCG lux doses (10 7 and 10 6 CFU per larvae) occurs despite no increase in mycobacterial growth, as a result of an overwhelming G. mellonella immune response at the site of infection.…”

“…Galleria mellonella insect larvae have increasingly been used as a surrogate to study host-pathogen interactions in a range of micro-organisms including Gram-positive and Gram-negative bacteria and fungi [11–14], and as a rapid model to screen novel antimicrobial drug candidates [15]. G. mellonella has a wide range of advantages that have made it a successful infection model.…”

“…They are easy to maintain at 37°C making them well-suited to studying human pathogens, and precise infection studies can be performed by injection without anaesthesia for testing the efficacy of small quantities of antimicrobial agents. In addition, G. mellonella are ethically more acceptable than the use of vertebrates meaning larger group sizes can be used to enhance reproducibility [11,15,19,20]. …”