Department of Surgery, Division of General and Acute Care Surgery, University of Texas Southwestern Medical Center , Dallas, TX, USA.
School of Biosciences, Institute of Microbiology and Infection, University of Birmingham , Birmingham, UK.
Virulence. 2020 Jan 1;11(1):695-706. doi: 10.1080/21505594.2020.1772652.
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 or . 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 and 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 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.
由于目前标准治疗药物的疗效不佳,手术部位感染的风险持续增加。需要新的方法来治疗或预防对抗生素耐药的细菌感染。多价黏附分子(MAM)是细菌毒力所必需的黏附素。我们使用与聚合物支架结合的重组 MAM 片段开发了一种细菌黏附抑制剂,模拟了细菌表面的 MAM7 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。使用手术感染的啮齿动物模型,将切口用具有抗药性的生物发光菌株 或 感染。用 MAM7 抑制剂或对照悬浮液治疗感染。在感染后九天定量细菌丰度。使用固定组织切片来表征炎症反应和组织学。MAM7 抑制剂处理使 和 的负担降低到检测阈值以下。用对照处理的组的细菌载量明显高于用 MAM7 抑制剂处理的组。抑制剂的治疗减少了手术感染模型中临床相关病原体的定植。使用 MAM7 抑制剂来阻止细菌在手术切口组织上的初始黏附可能会降低感染率,为减轻抗生素过度使用以预防手术部位感染提供了一种策略。