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Silk-Based Therapeutics Targeting Pseudomonas aeruginosa

机译：针对铜绿假单胞菌的基于丝绸的疗法

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Pseudomonas aeruginosa ( P. aeruginosa ) infections may lead to severe damage of the cornea, mucosa, and skin. The highly aggressive nature of P. aeruginosa and the rise in multi-drug resistance, particularly in nosocomial settings, lead to an increased risk for permanent tissue damage and potentially death. Thus, a growing need exists to develop alternative treatments to reduce both the occurrence of bacterial infection and biofilm development, as well as pathological progression post-infection. Silk derived from Bombyx mori silkworms serves as a unique biomaterial that is biocompatible with low immunogenicity and high versatility, and thereby ideal for stabilizing therapeutics. In this study, we assessed the cytotoxicity of P. aeruginosa on human corneal stromal stem cells and two mucosal cell lines (Caco-2 and HT29-MTX). To determine whether antibiotic-immobilized scaffolds can serve as alternative therapeutics to free, diffuse forms, we developed novel gentamicin-conjugated silk films as functional scaffolds and compared antimicrobial effects and free gentamicin. The advantages of generating a surface coating with a covalently-bound antibiotic may reduce potential side-effects associated with free gentamicin, as well as limit the diffusion of the drug. Our results suggest that gentamicin conjugated to native silk and carboxyl-enriched silk inhibits P. aeruginosa growth. Development of stabilized antibiotic treatments with surface toxicity selective against bacteria may serve as an alternative approach to treat active infections, as well as potential prophylactic use as coatings in high-risk cases, such as post-surgical complications or prolonged hospitalization.
机译：铜绿假单胞菌（P.aeruginosa）感染可能导致角膜，粘膜和皮肤严重受损。铜绿假单胞菌的高度侵袭性和多重耐药性的上升，尤其是在医院环境中，导致永久性组织损伤和潜在死亡的风险增加。因此，迫切需要开发替代疗法以减少细菌感染和生物膜形成的发生以及感染后的病理进展。桑蚕蚕丝是一种独特的生物材料，具有低免疫原性和高通用性，因此具有生物相容性，因此非常适合稳定治疗剂。在这项研究中，我们评估了铜绿假单胞菌对人角膜基质干细胞和两种粘膜细胞系（Caco-2和HT29-MTX）的细胞毒性。为了确定固定抗生素的支架是否可以作为游离，弥散形式的替代疗法，我们开发了新颖的庆大霉素偶联丝膜作为功能支架，并比较了抗菌作用和游离庆大霉素。用共价结合的抗生素产生表面涂层的优点可以减少与游离庆大霉素有关的潜在副作用，并限制药物的扩散。我们的结果表明庆大霉素与天然蚕丝和富含羧基的蚕丝结合可抑制铜绿假单胞菌的生长。具有选择性针对细菌的表面毒性的稳定抗生素治疗方法的开发，可以作为治疗活动性感染的替代方法，也可以作为高风险病例（如术后并发症或长期住院治疗）的涂层的潜在预防用途。

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