A Bombyx mori Infection Model for Screening Antibiotics against Staphylococcus epidermidis

SIMPLE SUMMARY: The use and misuse of antibiotics in the past decades have contributed to the wide spread of antibiotic resistance, which currently represents a major issue and threat to human health. Consequently, the discovery of new anti-infective molecules is of primary importance. In vivo studies are crucial for testing the efficacy of novel antibiotics. Invertebrate models look promising to reduce the large-scale use of mammalians, which is mainly limited by high costs and ethical concerns. In this scenario, the silkworm proved to be an interesting alternative among insects. Here, we developed a silkworm infection model by challenging the larvae with Staphylococcus epidermidis, one common cause of infections in hospitals, and assessing the curative effects of three life-saving glycopeptide antibiotics that are used to treat infections caused by multidrug-resistant Gram-positive pathogens. ABSTRACT: The increasing number of microorganisms that are resistant to antibiotics is prompting the development of new antimicrobial compounds and strategies to fight bacterial infections. The use of insects to screen and test new drugs is increasingly considered a promising tool to accelerate the discovery phase and limit the use of mammalians. In this study, we used for the first time the silkworm, Bombyx mori, as an in vivo infection model to test the efficacy of three glycopeptide antibiotics (GPAs), against the nosocomial pathogen Staphylococcus epidermidis. To reproduce the human physiological temperature, the bacterial infection was performed at 37 °C and it was monitored over time by evaluating the survival rate of the larvae, as well the response of immunological markers (i.e., activity of hemocytes, activation of the prophenoloxidase system, and lysozyme activity). All the three GPAs tested (vancomycin, teicoplanin, and dalbavancin) were effective in curing infected larvae, significantly reducing their mortality and blocking the activation of the immune system. These results corroborate the use of this silkworm infection model for the in vivo studies of antimicrobial molecules active against staphylococci.