Degasperi Margherita, Agostinis Chiara, Mardirossian Mario, Maschio Massimo, Taddio Andrea, Bulla Roberta, Scocchi Marco
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy.
Microorganisms. 2020 Sep 12;8(9):1407. doi: 10.3390/microorganisms8091407.
Most Cystic Fibrosis (CF) patients succumb to airway inflammation and pulmonary infections due to . -BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, was evaluated as a possible antibacterial aimed to address this issue. The antipseudomonal activity of -BMAP18 was tested in a pathophysiological context. The peptide displayed activity against CF isolates of in the presence of CF sputum when combined with sodium chloride and DNase I. In combination with DNase I, -BMAP18 discouraged the deposition of new biofilm and eradicated preformed biofilms of some strains. In addition, -BMAP18 down regulated the production of TNF-α, IL1-β, and TGF-β in LPS-stimulated or IFN-γ macrophages derived from THP-1 cells indicating an anti-inflammatory activity. The biocompatibility of -BMAP18 was assessed using four different cell lines, showing that residual cell-specific cytotoxicity at bactericidal concentrations could be abolished by the presence of CF sputum. Overall, this study suggests that -BMAP18 may be an interesting molecule as a starting point to develop a novel therapeutic agent to simultaneously contrast lung infections and inflammation in CF patients.
大多数囊性纤维化（CF）患者因……而死于气道炎症和肺部感染。-BMAP18是一种由D-氨基酸组成的可穿透细胞膜的抗菌肽，被评估为解决这一问题的一种可能的抗菌剂。在病理生理背景下测试了-BMAP18的抗铜绿假单胞菌活性。当与氯化钠和脱氧核糖核酸酶I联合使用时，该肽在存在CF痰液的情况下对CF分离株显示出活性。与脱氧核糖核酸酶I联合使用时，-BMAP18抑制了新生物膜的形成，并根除了一些菌株预先形成的生物膜。此外，-BMAP18下调了来自THP-1细胞的LPS刺激的或IFN-γ巨噬细胞中TNF-α、IL1-β和TGF-β的产生，表明其具有抗炎活性。使用四种不同的细胞系评估了-BMAP18的生物相容性，结果表明，CF痰液的存在可消除杀菌浓度下残留的细胞特异性细胞毒性。总体而言，这项研究表明，-BMAP18可能是一个有趣的分子，作为开发一种新型治疗剂的起点，以同时对抗CF患者的肺部感染和炎症。
