期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 71, 期 3, 页码 316-328出版社
WILEY
DOI: 10.1111/jphp.13034
关键词
IMPI; Pseudomonas aeruginosa secretome; Pseudolysin; LasB; ex vivo porcine wound model
资金
- Hessian Ministry of Science, Higher Education and Art
- BMBF via the project 4-IN
Objectives The objective of this study was to investigate the therapeutic potential of the insect metalloproteinase inhibitor (IMPI) from Galleria mellonella, the only known specific inhibitor of M4 metalloproteinases. Methods The fusion protein IMPI-GST (glutathione-S-transferase) was produced by fermentation in Escherichia coli and was tested for its ability to inhibit the proteolytic activity of the M4 metalloproteinases thermolysin and Pseudomonas elastase (PE), the latter a key virulence factor of the wound-associated and antibiotic-resistant pathogen Pseudomonas aeruginosa. We also tested the ability of IMPI to inhibit the secretome (Sec) of a P. aeruginosa strain obtained from a wound. Key findings We found that IMPI-GST inhibited thermolysin and PE in vitro and increased the viability of human keratinocytes exposed to Sec by inhibiting detachment caused by changes in cytoskeletal morphology. IMPI-GST also improved the cell migration rate in an in vitro wound assay and reduced the severity of necrosis caused by Sec in an ex vivo porcine wound model. Conclusions The inhibition of virulence factors is a novel therapeutic approach against antibiotic resistant bacteria. Our results indicate that IMPI is a promising drug candidate for the treatment of P. aeruginosa infections.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据