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抑制胶原酶Q1作为治疗皮肤伤口感染的新型抗毒力策略

Inhibition of Collagenase Q1 of as a Novel Antivirulence Strategy for the Treatment of Skin-Wound Infections.

作者信息

Alhayek Alaa, Khan Essak S, Schönauer Esther, Däinghaus Tobias, Shafiei Roya, Voos Katrin, Han Mitchell K L, Ducho Christian, Posselt Gernot, Wessler Silja, Brandstetter Hans, Haupenthal Jörg, Del Campo Aránzazu, Hirsch Anna K H

机构信息

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Helmholtz Centre for Infection Research (HZI) 38124 Saarbrücken, Germany; Department of Pharmacy Saarland University, Saarbrücken Campus Campus E8.1, 66123 Saarbrücken, Germany.

Leibniz Institute for New Materials (INM) Saarland University Campus D2 2, 66123 Saarbrücken, Germany.

出版信息

Adv Ther (Weinh). 2022 Mar;5(3):2100222. doi: 10.1002/adtp.202100222. Epub 2022 Jan 15.

Abstract

Despite the progress in surgical techniques and antibiotic prophylaxis, opportunistic wound infections with remain a public health problem. Secreted toxins are one of the main factors contributing to . pathogenicity. A promising strategy to treat such infections is to target these toxins and not the bacteria. Although the exoenzymes produced by . are thoroughly investigated, little is known about the role of . collagenases in wound infections. In this report, the collagenolytic activity of secreted collagenases (Col) is characterized in the . culture supernatant (csn) and its isolated recombinantly produced ColQ1 is characterized. The data reveals that ColQ1 causes damage on dermal collagen (COL). This results in gaps in the tissue, which might facilitate the spread of bacteria. The importance of . collagenases is also demonstrated in disease promotion using two inhibitors. Compound 2 shows high efficacy in peptidolytic, gelatinolytic, and COL degradation assays. It also preserves the fibrillar COLs in skin tissue challenged with ColQ1, as well as the viability of skin cells treated with . csn. A model highlights the significance of collagenase inhibition in vivo.

摘要

尽管手术技术和抗生素预防取得了进展,但机会性伤口感染仍然是一个公共卫生问题。分泌毒素是导致 致病性的主要因素之一。治疗此类感染的一个有前景的策略是针对这些毒素而非细菌。尽管对 产生的外切酶进行了深入研究,但对于 胶原酶在伤口感染中的作用知之甚少。在本报告中,对分泌型胶原酶(Col)在 培养上清液(csn)中的胶原olytic活性进行了表征,并对其重组产生的分离ColQ1进行了表征。数据显示ColQ1会对真皮胶原蛋白(COL)造成损伤。这导致组织中出现间隙,可能会促进细菌的传播。使用两种抑制剂在疾病促进方面也证明了 胶原酶的重要性。化合物2在肽水解、明胶水解和COL降解试验中显示出高效性。它还能在受到ColQ1挑战的皮肤组织中保留纤维状COL,以及在用 csn处理的皮肤细胞的活力。一个 模型突出了胶原酶抑制在体内的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a607/7612511/5d7734ea69ff/EMS141010-f001.jpg

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