Effective anti-infective therapies are required to offset the rise in antibiotic resistance. A novel vancomycin-innate defense regulator conjugate (V–IDR1018) was constructed with multimodal functionality, including bacterial killing, biofilm eradication, and immune modulation. The conjugate killed bacteria within 30 min, exhibited potent activity against persister cells, and showed no susceptibility to antimicrobial resistance in tissue culture assays. Additionally, it stimulated the release of chemokine MCP-1 and anti-inflammatory cytokine IL-10 and suppressed pro-inflammatory IL-1β from lipopolysaccharide-stimulated white blood cells. The conjugate demonstrated ∼90% eradication efficacy when assessed against the MRSA biofilm formed on an organoid human skin equivalent. Similarly, when evaluated in a murine, high-density skin abscess infection model using MRSA or Staphylococcus epidermidis, the conjugate decreased dermonecrosis and reduced bacterial load. The exceptional in vitro and in vivo efficacy of the conjugate, in addition to its safety profile, makes it a valuable candidate to treat complex infectious diseases.

中文翻译：

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多功能抗生素-宿主防御肽偶联物可杀死细菌、根除生物膜并调节先天免疫反应

需要有效的抗感染疗法来抵消抗生素耐药性的上升。构建了一种具有多模式功能的新型万古霉素先天防御调节剂偶联物 (V-IDR1018)，包括细菌杀灭、生物膜根除和免疫调节。该偶联物在 30 分钟内杀死细菌，表现出对持久细胞的有效活性，并且在组织培养试验中显示出对抗菌素耐药性的敏感性。此外，它还刺激趋化因子 MCP-1 和抗炎细胞因子 IL-10 的释放，并抑制脂多糖刺激的白细胞中的促炎 IL-1β。当针对在类器官人体皮肤等效物上形成的 MRSA 生物膜进行评估时，该缀合物显示出约 90% 的根除功效。同样，当在小鼠中评估时，表皮葡萄球菌，缀合物减少皮肤坏死并减少细菌负荷。除了其安全性之外，缀合物的卓越的体外和体内功效使其成为治疗复杂传染病的有价值的候选者。