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在人载脂蛋白 B 中鉴定出的隐秘蛋白可作为治疗囊性纤维化病中抗生素耐药性的新武器。

Cryptides Identified in Human Apolipoprotein B as New Weapons to Fight Antibiotic Resistance in Cystic Fibrosis Disease.

机构信息

Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy.

Istituto Nazionale di Biostrutture e Biosistemi (INBB), I-00136 Rome, Italy.

出版信息

Int J Mol Sci. 2020 Mar 17;21(6):2049. doi: 10.3390/ijms21062049.

Abstract

Chronic respiratory infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients, and are characterized by the development of multidrug resistance (MDR) phenotype and biofilm formation, generally recalcitrant to treatment with conventional antibiotics. Hence, novel effective strategies are urgently needed. Antimicrobial peptides represent new promising therapeutic agents. Here, we analyze for the first time the efficacy of three versions of a cryptide identified in human apolipoprotein B (ApoB, residues 887-922) towards bacterial strains clinically isolated from CF patients. Antimicrobial and anti-biofilm properties of ApoB-derived cryptides have been analyzed by broth microdilution assays, crystal violet assays, confocal laser scanning microscopy and scanning electron microscopy. Cell proliferation assays have been performed to test cryptide effects on human host cells. ApoB-derived cryptides have been found to be endowed with significant antimicrobial and anti-biofilm properties towards and strains clinically isolated from CF patients. Peptides have been also found to be able to act in combination with the antibiotic ciprofloxacin, and they are harmless when tested on human bronchial epithelial mesothelial cells. These findings open interesting perspectives to cryptide applicability in the treatment of chronic lung infections associated with CF disease.

摘要

慢性呼吸道感染是囊性纤维化 (CF) 患者发病和死亡的主要原因,其特征是多药耐药 (MDR) 表型和生物膜形成,通常对常规抗生素治疗有抗性。因此,迫切需要新的有效策略。抗菌肽是一种很有前途的新型治疗药物。在这里,我们首次分析了在人载脂蛋白 B (ApoB,残基 887-922) 中鉴定出的三种隐肽对从 CF 患者中临床分离的细菌株的疗效。通过肉汤微量稀释法、结晶紫法、共聚焦激光扫描显微镜和扫描电子显微镜分析了 ApoB 衍生隐肽的抗菌和抗生物膜特性。进行细胞增殖试验以测试隐肽对人宿主细胞的影响。发现 ApoB 衍生的隐肽对 和 具有显著的抗菌和抗生物膜特性,这些细菌株是从 CF 患者中临床分离出来的。还发现这些肽能够与抗生素环丙沙星联合使用,并且在测试对人支气管上皮间皮细胞的毒性时是无害的。这些发现为隐肽在治疗与 CF 疾病相关的慢性肺部感染方面的应用开辟了有趣的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149b/7139702/1ae8a67ffe34/ijms-21-02049-g001.jpg

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