<i>Galleria mellonella</i> as an infection model for the virulent <i>Mycobacterium tuberculosis</i> H37Rv

Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>MTB</i>), 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 <i>Galleria mellonella</i> (the greater wax moth, <i>Gm</i>) larvae can be used as a low cost, rapid, and ethically more acceptable model for TB research. This is the first study to infect <i>Gm</i> with the fully virulent <i>MTB</i> H37Rv, the most widely used strain in research. Infection of <i>Gm</i> with <i>MTB</i> resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated <i>Mycobacterium bovis</i> BCG and auxotrophic <i>MTB</i> strains. The <i>Gm-MTB</i> model can also be used for anti-TB drug screening, although CFU enumeration from <i>Gm</i> is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of <i>MTB</i> isogenic mutants can be determined in <i>Gm</i>. However, comparison of mutant phenotypes in <i>Gm</i> against conventional models must consider the limitations of innate immunity. Our findings indicate that <i>Gm</i> will be a practical, valuable, and advantageous additional model to be used alongside existing models to advance tuberculosis research.