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首页> 外文期刊>EBioMedicine >Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo
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Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo

机译：针对DNABII蛋白的DNA结合末端的单克隆抗体会在体外破坏生物膜并在体内诱导细菌清除

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The vast majority of chronic and recurrent bacterial diseases are attributed to the presence of a recalcitrant biofilm that contributes significantly to pathogenesis. As such, these diseases will require an innovative therapeutic approach. We targeted DNABII proteins, an integral component of extracellular DNA (eDNA) which is universally found as part of the pathogenic biofilm matrix to develop a biofilm disrupting therapeutic. We show that a cocktail of monoclonal antibodies directed against specific epitopes of a DNABII protein is highly effective to disrupt diverse biofilms in vitro as well as resolve experimental infection in vivo, in both a chinchilla and murine model. Combining this monoclonal antibody cocktail with a traditional antibiotic to kill bacteria newly released from the biofilm due to the action of the antibody cocktail was highly effective. Our results strongly support these monoclonal antibodies as attractive candidates for lead optimization as a therapeutic for resolution of bacterial biofilm diseases.
机译：绝大多数慢性和复发性细菌性疾病归因于顽强的生物膜的存在，该膜对发病机理有重大贡献。因此，这些疾病将需要创新的治疗方法。我们靶向DNABII蛋白，它是细胞外DNA（eDNA）的组成部分，普遍被发现是致病性生物膜基质的一部分，以开发破坏治疗的生物膜。我们显示针对针对DNABII蛋白的特定表位的单克隆抗体混合物在黄鼠和鼠模型中，对破坏体外各种生物膜以及解决体内实验性感染非常有效。将该单克隆抗体混合物与传统抗生素组合以杀死由于抗体混合物的作用而从生物膜新释放的细菌非常有效。我们的结果有力地支持了这些单克隆抗体作为引诱物优化的有吸引力的候选物，以解决细菌生物膜疾病。

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