<i>Galleria mellonella -</i> a novel infection model for the <i>Mycobacterium tuberculosis</i> complex

Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative <i>in vivo</i> models. The insect larvae, <i>Galleria mellonella</i> has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections. Here we report for the first time that <i>G. mellonella</i> can be used as an infection model for members of the <i>Mycobacterium tuberculosis</i> complex. We demonstrate a dose-response for <i>G. mellonella</i> survival infected with different inocula of bioluminescent <i>Mycobacterium bovis</i> BCG <i>lux</i>, and demonstrate suppression of mycobacterial luminesence over 14 days. Histopathology staining and transmission electron microscopy of infected <i>G. mellonella</i> phagocytic haemocytes show internalization and aggregation of <i>M. bovis</i> BCG <i>lux</i> in granuloma-like structures, and increasing accumulation of lipid bodies within <i>M. bovis</i> BCG <i>lux</i> over time, characteristic of latent tuberculosis infection. Our results demonstrate <i>that G. mellonella</i> can act as a surrogate host to study the pathogenesis of mycobacterial infection and shed light on host-mycobacteria interactions, including latent tuberculosis infection.