ROS-dependent innate immune mechanisms control Staphylococcus aureus MRSA virulence in the Drosophila larval model

Abstract

Antibiotics multi-resistant Staphylococcus aureus strains constitute a major public health concern worldwide and are responsible of both healthcare- and community-associated infections. Here we have established a robust and simple S. aureus oral infection model, using Drosophila melanogaster larva, which allowed to follow S. aureus fate at the whole organism level as well as the host immune responses. Fluorescence microscopy and Light sheet 3D imaging revealed bacterial clustering at the posterior midgut that displays neutral pH. Our study demonstrates that S. aureus infection triggers host H2O2 production through Duox enzyme, consequently empowering antimicrobial peptides production through Toll pathway activation. We also show that catalase-mediated quenching of H2O2 not only enhances S. aureus survival but also minimizes host antimicrobial response, hence reducing bacterial clearance in vivo. Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capacities of two other bacterial pathogens: Salmonella Typhimurium and Shigella flexneri. Overall, the drosophila larva may constitute a general model to follow in vivo host innate immune responses triggered upon infection with human pathogens.