Inducing bacterial calcification for systematic treatment and immunomodulation against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the deadliest bacteria globally due to antibiotic resistance. In this study, we crosslinked antigen-binding fragments of monoclonal antibodies against the wall-teichoic acid of S. aureus with polysialic acid to form an antibody‒PSA conjugate, which can effectively target and induce calcification on the surface of MRSA. This process eliminates bacteria by hindering the energy metabolism and multiple essential metabolic pathways of MRSA. We found that bacterial calcification leads to increased expression of calprotectin, S100A8/S100A9, in macrophages and monocytes in vivo and can stimulate the activation of macrophages to an inflammatory state, thereby promoting bacterial eradication as an immunomodulator. Systemic administration of the antibody‒PSA conjugate demonstrates high efficacy and safety for treating chronic lung infections and chronic osteomyelitis caused by MRSA in mice. This study offers a promising therapy for treating drug-resistant bacteria and related refractory pathogenic infections.