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使用棘白菌素类作为治疗尿路感染的一种潜在方法。

Use of ceragenins as a potential treatment for urinary tract infections.

机构信息

Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland.

Department of Microbiology and Immunology, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, 25-001, Kielce, Poland.

出版信息

BMC Infect Dis. 2019 May 2;19(1):369. doi: 10.1186/s12879-019-3994-3.

DOI:10.1186/s12879-019-3994-3
PMID:31046689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6498624/
Abstract

BACKGROUND

Urinary tract infections (UTIs) are one of the most common bacterial infections. High recurrence rates and the increasing antibiotic resistance among uropathogens constitute a large social and economic problem in current public health. We assumed that combination of treatment that includes the administration ceragenins (CSAs), will reinforce the effect of antimicrobial LL-37 peptide continuously produced by urinary tract epithelial cells. Such treatment might be an innovative approach to enhance innate antibacterial activity against multidrug-resistant E. coli.

METHODS

Antibacterial activity measured using killing assays. Biofilm formation was assessed using crystal violet staining. Viability of bacteria and bladder epithelial cells subjected to incubation with tested agents was determined using MTT assays. We investigated the effects of chosen molecules, both alone and in combinations against four clinical strains of E. coli, obtained from patients diagnosed with recurrent UTI.

RESULTS

We observed that the LL-37 peptide, whose concentration increases at sites of urinary infection, exerts increased bactericidal effect against E. coli when combined with ceragenins CSA-13 and CSA-131.

CONCLUSION

We suggest that the employment of combination of natural peptide LL-37 with synthetic analogs might be a potential solution to treat urinary tract infections caused by drug-resistant bacteria.

摘要

背景

尿路感染(UTIs)是最常见的细菌感染之一。尿路感染病原体的高复发率和不断增加的抗生素耐药性,构成了当前公共卫生领域的一个重大社会和经济问题。我们假设,包括施用杀菌素(CSAs)在内的联合治疗方案,将增强尿路上皮细胞持续产生的抗菌肽 LL-37 的作用。这种治疗方法可能是增强针对多药耐药大肠杆菌的先天抗菌活性的一种创新方法。

方法

使用杀菌试验测量抗菌活性。使用结晶紫染色评估生物膜形成。使用 MTT 测定法测定经测试剂孵育的细菌和膀胱上皮细胞的活力。我们研究了所选分子单独和联合对从复发性尿路感染患者中获得的四种临床大肠杆菌菌株的作用。

结果

我们观察到,在尿路感染部位增加的 LL-37 肽与杀菌素 CSA-13 和 CSA-131 联合使用时,对大肠杆菌表现出增强的杀菌作用。

结论

我们认为,天然肽 LL-37 与合成类似物的联合使用可能是治疗由耐药菌引起的尿路感染的一种潜在解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/0c7694c83702/12879_2019_3994_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/ad2ba43535bb/12879_2019_3994_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/e6e8b2dc3eca/12879_2019_3994_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/dbc146fa44a1/12879_2019_3994_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/fa5709a16436/12879_2019_3994_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/8560376d39d1/12879_2019_3994_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/0c7694c83702/12879_2019_3994_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/ad2ba43535bb/12879_2019_3994_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/e6e8b2dc3eca/12879_2019_3994_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/dbc146fa44a1/12879_2019_3994_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/fa5709a16436/12879_2019_3994_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/8560376d39d1/12879_2019_3994_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888d/6498624/0c7694c83702/12879_2019_3994_Fig6_HTML.jpg

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