Pathogen-targeting biomineralized bacterial outer membrane vesicles for eradicating both intracellular and extracellular Staphylococcus aureus.

Intracellular Staphylococcus aureus is associated with recurrent infections and antibiotic resistance. Conventional antibiotics are ineffective against such intracellular bacterial pathogens, which calls for exploration of new approaches to treat these infections. Here, we report the development of pathogen-targeting biomineralized bacterial outer membrane vesicle (OMV) for targeted antibiotic delivery and eradicating both intracellular and extracellular S. aureus. These OMVs were derived from E. coli, and chemically modified with hydroxamate-type siderophore to target the intracellular S. aureus. The surface of OMV was coated with pH-sensitive calcium carbonate (CaCO) to target the infection microenvironment. The CaCO-coated siderophore-OMV (SOMV@CaCO) was loaded with the antimicrobial drugs lysostaphin (Lsn) and mupirocin (Mup) (Lsn-SOMV@CaCO-Mup) and administration of these OMVs resulted in effective eradication of both extracellular and intracellular S. aureus. Thus, Lsn-SOMV@CaCO-Mup provides a novel and promising strategy for the treatment of invasive S. aureus infections.