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囊性纤维化的潜在新型治疗策略:天然和设计的α-螺旋肽对金黄色葡萄球菌、铜绿假单胞菌和嗜麦芽窄食单胞菌的抗菌和抗生物膜活性。

Potential novel therapeutic strategies in cystic fibrosis: antimicrobial and anti-biofilm activity of natural and designed α-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia.

机构信息

Department of Biomedical Sciences, "G. d'Annunzio" University of Chieti, Via Vestini 31, 66100 Chieti, Italy.

出版信息

BMC Microbiol. 2012 Jul 23;12:145. doi: 10.1186/1471-2180-12-145.

Abstract

BACKGROUND

Treatment of cystic fibrosis-associated lung infections is hampered by the presence of multi-drug resistant pathogens, many of which are also strong biofilm producers. Antimicrobial peptides, essential components of innate immunity in humans and animals, exhibit relevant in vitro antimicrobial activity although they tend not to select for resistant strains.

RESULTS

Three α-helical antimicrobial peptides, BMAP-27 and BMAP-28 of bovine origin, and the artificial P19(9/B) peptide were tested, comparatively to Tobramycin, for their in vitro antibacterial and anti-biofilm activity against 15 Staphylococcus aureus, 25 Pseudomonas aeruginosa, and 27 Stenotrophomonas maltophilia strains from cystic fibrosis patients. All assays were carried out in physical-chemical experimental conditions simulating a cystic fibrosis lung. All peptides showed a potent and rapid bactericidal activity against most P. aeruginosa, S. maltophilia and S. aureus strains tested, at levels generally higher than those exhibited by Tobramycin and significantly reduced biofilm formation of all the bacterial species tested, although less effectively than Tobramycin did. On the contrary, the viability-reducing activity of antimicrobial peptides against preformed P. aeruginosa biofilms was comparable to and, in some cases, higher than that showed by Tobramycin.

CONCLUSIONS

The activity shown by α-helical peptides against planktonic and biofilm cells makes them promising "lead compounds" for future development of novel drugs for therapeutic treatment of cystic fibrosis lung disease.

摘要

背景

囊性纤维化相关肺部感染的治疗受到多药耐药病原体的阻碍,其中许多病原体也是强生物膜生产者。抗菌肽是人类和动物先天免疫的重要组成部分,具有相关的体外抗菌活性,尽管它们往往不会选择耐药菌株。

结果

三种α-螺旋抗菌肽,牛源的 BMAP-27 和 BMAP-28 以及人工 P19(9/B)肽,与妥布霉素相比,在模拟囊性纤维化肺部的物理化学实验条件下,针对来自囊性纤维化患者的 15 株金黄色葡萄球菌、25 株铜绿假单胞菌和 27 株嗜麦芽窄食单胞菌进行了体外抗菌和抗生物膜活性测试。所有试验均针对大多数测试的 P. aeruginosa、S. maltophilia 和 S. aureus 菌株进行了测试,所有肽均表现出强大而快速的杀菌活性,其水平通常高于妥布霉素,并且显著降低了所有测试细菌的生物膜形成,尽管不如妥布霉素有效。相反,抗菌肽对已形成的 P. aeruginosa 生物膜的降低活力活性与妥布霉素相当,在某些情况下甚至高于妥布霉素。

结论

α-螺旋肽对浮游和生物膜细胞的活性使其成为未来开发用于治疗囊性纤维化肺部疾病的新型药物的有前途的“先导化合物”。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/258e/3416647/a92e635b043e/1471-2180-12-145-1.jpg

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