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三种 生物膜 内源性胞外多聚物(Psl、Pel 和 Alginate)如何各自被利用于囊性纤维化肺部感染的抗生素佐剂效应。

How Three Self-Secreted Biofilm Exopolysaccharides of , Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.

机构信息

Department of Translational Medicine, Research Institute, The Hospital for Sick Children, University of Toronto, 686 Bay Street, Toronto, ON M5G 0A4, Canada.

Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada.

出版信息

Int J Mol Sci. 2023 May 13;24(10):8709. doi: 10.3390/ijms24108709.

Abstract

In cystic fibrosis (CF), pulmonary infection with is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to their failure to eradicate infection but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of , wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. The three biofilm-associated EPSs secreted by (alginate, Psl, and Pel) are each under investigation and are being exploited in ways that potentiate antibiotics. In this review, we describe the development and structure of biofilms before examining each EPS as a potential therapeutic target for combating pulmonary infection with in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

摘要

在囊性纤维化(CF)中,感染 是导致发病率和死亡率增加的原因,特别是对于那些感染变得慢性化且依赖长期抑制性治疗的患者。目前的抗生素虽然在机制和给药方式上有所不同,但不仅由于它们未能根除感染,而且由于它们不能阻止肺功能随时间下降的进展,因此是不够的。造成这种失败的原因之一被认为是 的生物膜生长方式,其中自我分泌的胞外多糖(EPS)为抗生素提供物理保护,并产生一系列具有代谢和表型异质性的小生境。 由 分泌的三种与生物膜相关的 EPS(藻酸盐、Psl 和 Pel)都在被研究中,并以增强抗生素的方式被利用。在这篇综述中,我们描述了 的生物膜的发展和结构,然后检查每个 EPS 作为对抗 CF 中 肺部感染的潜在治疗靶点,特别关注这些新兴疗法的当前证据以及将这些疗法推向临床的障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3902/10218432/07f3d64b6465/ijms-24-08709-g001.jpg

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