Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model.
Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model.
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DOI：
10.1080/21505594.2020.1772652
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Krachler AM
中科院分区：
文献类型：
--
作者：
Huebinger RM;Do DH;Carlson DL;Yao X;Stones DH;De Souza Santos M;Vaz DP;Keen E;Wolf SE;Minei JP;Francis KP;Orth K;Krachler AM
由于当前标准治疗药物缺乏疗效，手术部位感染风险持续增加。需要治疗或预防耐药性细菌感染的新方法。多价粘附分子（MAM）是细菌毒力所需的粘附素。我们开发了一种细菌粘附抑制剂，使用结合到聚合物支架上的重组MAM片段，模拟MAM7在细菌表面的展示。在这里，我们测试MAM7抑制剂预防革兰氏阳性和革兰氏阴性感染的功效。使用外科感染的啮齿动物模型，用金黄色葡萄球菌或铜绿假单胞菌的耐药性生物发光菌株感染切口部位。感染用MAM7抑制剂或对照悬浮液处理。感染后9天定量细菌丰度。使用固定的组织切片表征炎症反应和组织学。MAM7抑制剂处理降低了S.金黄色葡萄球菌和铜绿假单胞菌低于检测阈值。用对照处理的组的细菌负荷显著高于MAM7载体处理的组。用抑制剂治疗减少了手术感染的体内模型中临床相关病原体的定殖。使用MAM7抑制剂阻断手术切口中细菌对组织的初始粘附可能会降低感染率，这是一种减轻抗生素过度使用以预防手术部位感染的策略。
Surgical site infection risk continues to increase due to lack of efficacy in current standard of care drugs. New methods to treat or prevent antibiotic-resistant bacterial infections are needed. Multivalent Adhesion Molecules (MAM) are bacterial adhesins required for virulence. We developed a bacterial adhesion inhibitor using recombinant MAM fragment bound to polymer scaffold, mimicking MAM7 display on the bacterial surface. Here, we test MAM7 inhibitor efficacy to prevent Gram-positive and Gram-negative infections. Using a rodent model of surgical infection, incision sites were infected with antibiotic-resistant bioluminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa. Infections were treated with MAM7 inhibitor or control suspension. Bacterial abundance was quantified for nine days post infection. Inflammatory responses and histology were characterized using fixed tissue sections. MAM7 inhibitor treatment decreased burden of S. aureus and P. aeruginosa below detection threshold. Bacterial load of groups treated with control were significantly higher than MAM7 inhibitor-treated groups. Treatment with inhibitor reduced colonization of clinically-relevant pathogens in an in vivo model of surgical infection. Use of MAM7 inhibitor to block initial adhesion of bacteria to tissue in surgical incisions may reduce infection rates, presenting a strategy to mitigate overuse of antibiotics to prevent surgical site infections.