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针对 DNABII 蛋白整合宿主因子(IHF)的抗体抑制窦道植入物生物膜。

Antibodies against the DNABII protein integration host factor (IHF) inhibit sinus implant biofilms.

机构信息

Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

Department of Pediatric Otolaryngology, Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

出版信息

Laryngoscope. 2020 Jun;130(6):1364-1371. doi: 10.1002/lary.28188. Epub 2019 Jul 17.

Abstract

OBJECTIVES

Chronic rhinosinusitis is a common, costly condition often treated with endoscopic sinus surgery and intraoperative placement of intranasal sinus implant materials. Whereas these materials aid in postoperative healing, they also support bacterial biofilm formation and thus contribute to negative outcomes. This study examined pretreatment of sinus implant materials with antibody against an essential bacterial biofilm structural component, the DNABII family of DNA-binding proteins, as a strategy to prevent biofilm formation.

METHODS

Sinus implant materials were equilibrated in immunoglobulin G (IgG)-enriched antiserum against the DNABII protein integration host factor (IHF), individually or in combination with amoxicillin-clavulanate prior to inoculation with nontypeable Haemophilus influenzae (NTHI), a predominant pathogen of chronic rhinosinusitis. After 16 hours, the bacterial burden was quantitated and compared to pretreatment with saline, IgG-enriched naive serum, or amoxicillin-clavulanate alone.

RESULTS

NTHI readily formed biofilms on all three materials in vitro. However, pretreatment of each material with IgG-enriched anti-IHF resulted in a significant decrease in bacterial burden compared to controls (P ≤ 0.05). Moreover, a significant and synergistic outcome was achieved with a cocktail of anti-IHF plus amoxicillin-clavulanate (P ≤ 0.05) with complete inhibition of NTHI biofilm formation on all three materials.

CONCLUSIONS

Biofilm formation was well supported in vitro on three sinus implant materials that vary in composition and resorption characteristics; however, pretreatment of each with DNABII protein targeted antibodies in combination with a previously ineffective antibiotic was highly effective to prevent the formation NTHI biofilms. These data demonstrate the potential for clinical utility of pretreatment of sinus implant and additional surgical materials with anti-DNABII antibodies.

LEVEL OF EVIDENCE

NA Laryngoscope, 130:1364-1371, 2020.

摘要

目的

慢性鼻-鼻窦炎是一种常见的、代价高昂的疾病,常采用鼻内镜鼻窦手术和术中放置鼻腔鼻窦植入材料进行治疗。虽然这些材料有助于术后愈合,但它们也支持细菌生物膜的形成,从而导致不良后果。本研究检查了用针对细菌生物膜结构成分(DNABII 家族 DNA 结合蛋白)的抗体预处理鼻窦植入材料,作为预防生物膜形成的一种策略。

方法

将鼻窦植入材料分别用富含 IgG 的抗 DNAII 蛋白整合宿主因子(IHF)抗血清或与阿莫西林-克拉维酸联合预处理,然后接种非典型流感嗜血杆菌(NTHI),NTHI 是慢性鼻-鼻窦炎的主要病原体。16 小时后,定量细菌负荷并与生理盐水、富含 IgG 的天然血清或单独阿莫西林-克拉维酸预处理进行比较。

结果

NTHI 在所有三种材料上都很容易形成生物膜。然而,与对照组相比,用富含 IgG 的抗 IHF 预处理每种材料都导致细菌负荷显著降低(P≤0.05)。此外,抗 IHF 加阿莫西林-克拉维酸鸡尾酒疗法(P≤0.05)产生了显著的协同作用,完全抑制了所有三种材料上 NTHI 生物膜的形成。

结论

三种组成和吸收特性不同的鼻窦植入材料在体外都能很好地支持生物膜形成;然而,用靶向 DNAII 蛋白的抗体预处理每种材料,并结合以前无效的抗生素,可高度有效地预防 NTHI 生物膜的形成。这些数据表明,用抗 DNAII 抗体预处理鼻窦植入和其他外科材料具有潜在的临床应用价值。

证据水平

NA 喉镜,130:1364-1371,2020。

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