Galleria mellonella model recapitulates Staphylococcus aureus hemolysin toxicity and antibody-mediated mechanisms of protection

The study of host-pathogen interactions in animal infection models has clarified mechanisms of bacterial pathogenicity and supported the development of preventive and therapeutic strategies. Although many virulence factors have been identified in vivo using mammals such as mice and rats, this work requires large numbers of animals. Over the past two decades, insect-based alternatives have gained popularity due to ethical and practical advantages. This study evaluated Galleria mellonella larvae as an alternative in vivo model for investigating microbial pathogenicity, focusing on Staphylococcus aureus and its conserved toxin alpha-haemolysin (Hla). Larvae were injected with purified Hla or infected with bacteria, and survival, clinical scores, and bacterial burden were monitored. Results showed that larvae are susceptible to Hla-mediated toxicity, whether the toxin is administered directly or produced during infection. Notably, pre-treatment with a human anti-Hla monoclonal antibody protected larvae from toxin-induced disease and staphylococcal infection, similarly to what is reported in more extensively studied mammal models. These findings support Galleria mellonella as a cost-effective, ethical model for studying pathogenicity, characterizing virulence factors, and evaluating targeted treatments such as monoclonal antibodies. When combined with high-throughput in vitro assays, this approach may accelerate the discovery of new therapeutic and preventive interventions while reducing reliance on mammalian models.