Spermidine Associated\nwith Gut Microbiota Protects\nAgainst MRSA Bloodstream Infection by Promoting Macrophage M2 Polarization

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that causes various diseases. Extensive\nresearches highlight the significant role of gut microbiota and its\nmetabolites, particularly spermidine, in infectious diseases. However,\nthe immunomodulatory mechanisms of spermidine in MRSA-induced bloodstream\ninfection remain unclear. Here, we confirmed the protective effects\nof spermidine in bloodstream infection in mice. Spermidine reduced\nthe bacterial load and expression of inflammatory factors by shifting\nthe macrophage phenotype to an anti-inflammatory phenotype, ultimately\nprolonging the survival of the infected mice. The protective effect\nagainst MRSA infection may rely on the elevated expression of protein\ntyrosine phosphatase nonreceptor 2 (PTPN2). Collectively, these findings\nconfirm the immunoprotective effects of spermidine via binding to\nPTPN2 in MRSA bloodstream infection, providing new ideas for the treatment\nof related infectious diseases.