Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer which has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity which can normalize rheologic properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, which may warrant further evaluation as a therapeutic.

中文翻译：

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聚（乙酰，精氨酰）氨基葡萄糖破坏铜绿假单胞菌生物膜并增强大鼠肺部感染模型中的细菌清除

铜绿假单胞菌是一种常见的机会性病原体，可导致多种疾病状态的慢性感染，包括囊性纤维化 (CF) 和非 CF 支气管扩张患者的呼吸道感染。像许多机会主义者一样，铜绿假单胞菌形成多细胞生物膜群落，被广泛认为是慢性/复发性感染期间细菌持久性和对抗菌剂和宿主免疫效应物的耐药性的重要决定因素。聚（乙酰，精氨酰）葡糖胺 (PAAG) 是一种糖聚合物，它对多种细菌种类具有抗菌活性，并且还具有粘液溶解活性，可以使囊性纤维化粘液的流变特性正常化。在这项研究中，我们试图评估 PAAG 对铜绿假单胞菌的影响体外生物膜内的细菌，以及啮齿动物感染模型中实验性肺部感染的背景。PAAG 处理对铜绿假单胞菌生物膜产生显着的杀菌活性，并减少非生物表面以及永生化囊性纤维化人支气管上皮细胞表面上预制铜绿假单胞菌生物膜的总生物量。膜完整性研究表明，PAAG 会导致铜绿假单胞菌细胞形态发生变化并失调膜极性。PAAG 治疗减少了实验性铜绿假单胞菌的感染和随之而来的组织炎症鼠感染。基于这些发现，我们得出结论，PAAG 代表了一种对抗铜绿假单胞菌感染的新方法，这可能需要进一步评估作为治疗方法。