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合成肽KP及其衍生物对产生物膜的头孢菌素耐药菌株的活性

Activity of Synthetic Peptide KP and Its Derivatives against Biofilm-Producing Strains Resistant to Cephalosporins.

作者信息

Artesani Lorenza, Ciociola Tecla, Vismarra Alice, Bacci Cristina, Conti Stefania, Giovati Laura

机构信息

Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.

Microbiome Research Hub, University of Parma, 43124 Parma, Italy.

出版信息

Antibiotics (Basel). 2024 Jul 24;13(8):683. doi: 10.3390/antibiotics13080683.

Abstract

Bacterial resistance to β-lactam antibiotics, particularly new generation cephalosporins, is a major public health concern. In , resistance to these antibiotics is mainly mediated by extended-spectrum β-lactamases (ESBL), which complicates a range of health-threatening infections. These infections may also be biofilm-related, making them more difficult to treat because of the higher tolerance to conventional antibiotics and the host immune response. In this study, we tested as potential new drug candidates against biofilm-forming ESBL-producing four antimicrobial peptides previously shown to have antifungal properties. The peptides proved to be active in vitro at micromolar concentrations against both sensitive and ESBL-producing strains, effectively killing planktonic cells and inhibiting biofilm formation. Quantitative fluorescence intensity analysis of three-dimensional reconstructed confocal laser scanning microscopy (CLSM) images of mature biofilm treated with the most active peptide showed significant eradication and a reduction in viable bacteria, while scanning electron microscopy (SEM) revealed gross morphological alterations in treated bacteria. The screening of the investigated peptides for antibacterial and antibiofilm activity led to the selection of a leading candidate to be further studied for developing new antimicrobial drugs as an alternative treatment against microbial infections, primarily associated with biofilms.

摘要

细菌对β-内酰胺类抗生素,尤其是新一代头孢菌素的耐药性是一个重大的公共卫生问题。在……中,对这些抗生素的耐药性主要由超广谱β-内酰胺酶(ESBL)介导,这使一系列威胁健康的感染变得复杂。这些感染也可能与生物膜有关,由于对传统抗生素的耐受性更高以及宿主免疫反应,使得它们更难治疗。在本研究中,我们测试了四种先前已显示具有抗真菌特性的抗菌肽作为针对产生生物膜的产ESBL菌的潜在新药候选物。这些肽在微摩尔浓度下对敏感菌株和产ESBL菌株在体外均有活性,能有效杀死浮游细胞并抑制生物膜形成。用活性最强的肽处理成熟生物膜后,对三维重建共聚焦激光扫描显微镜(CLSM)图像进行定量荧光强度分析,结果显示有显著的根除效果且活菌数量减少,而扫描电子显微镜(SEM)显示处理后的细菌出现明显的形态改变。对所研究的肽进行抗菌和抗生物膜活性筛选后,选出了一个主要候选物,将进一步研究以开发新型抗菌药物,作为针对主要与生物膜相关的微生物感染的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3556/11350827/64a3e1431506/antibiotics-13-00683-g001.jpg

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