Identification of new dermaseptins with self-assembly tendency: membrane disruption, biofilm eradication, and infected wound healing efficacy
Identification of new dermaseptins with self-assembly tendency: membrane disruption, biofilm eradication, and infected wound healing efficacy
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具有自组装倾向的新型皮肤抗菌肽的鉴定：膜破坏、生物膜根除和感染伤口愈合功效
DOI：
10.1016/j.actbio.2020.03.024
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发表时间：
2020
影响因子：
9.7
通讯作者：
Gao Yitian
中科院分区：
文献类型：
--
作者：
Song Xinyu;Pan Hanling;Wang Hanfei;Liao Xiaoying;Sun Da;Xu Ke;Chen Tianbao;Zhang Xu;Wu Mingjiang;Wu Di;Gao Yitian
与抗生素耐药细菌和生物膜相关的严重感染引起了越来越多的关注，因为这些疾病很难用目前的抗生素治疗。典型的阳离子抗菌肽皮抑菌肽因其抗菌谱广、副作用小而被认为是最有前途的下一代抗生素。通过鸟枪法克隆蜡质猴树蛙（Phyllomedusasauvagei）皮肤分泌物中的皮抑肽（dermaseptin）基因，发现了两种新的皮抑肽DMS-PS1和DMS-PS2。从皮肤分泌物中分离出从克隆的cDNA预测的成熟肽序列，并通过质谱法确认。评估化学合成的重复样品的各种生物活性。这两种皮肽都对包括抗生素耐药细菌在内的广谱微生物有效，并对革兰氏阳性和革兰氏阴性细菌生物膜表现出显着的效力，对哺乳动物红细胞的毒性较低。值得注意的是，DMS-PS2对由诱导伤口引起的耐甲氧西林金黄色葡萄球菌引起的小鼠皮肤感染有效。DMS-PS2的作用方式为膜透化作用。总体而言，这些数据提供了令人信服的证据，抗感染剂和/或生物材料作为一种新的治疗方法对细菌infection.Statement的显著性细菌粘附生物材料的发展仍然是一个主要问题。抗微生物肽（AMP）是先天免疫系统的众所周知的组分，其可用于克服生物膜相关的感染。阳离子皮抑菌肽显示出显著的广谱抗微生物活性和对持续性感染的细菌生物膜的活性，并且对哺乳动物红细胞具有弱毒性。DMS-PS2的膜透化能力得到证实，并且重要的是，它证明了治疗MRSA感染的鼠皮肤模型的有效效率。此外，出乎我们的意料，DMS-PS2显示出自聚集参数，表明固定化AMP在临床应用中具有很好的潜力。这也使其成为抗感染生物材料开发的有希望的建议。
Severe infections associated with antibiotic-resistant bacteria and biofilms have attracted increasing interest as these diseases are difficult to treat with current antibiotics. Typical cationic antimicrobial peptides dermaseptins are considered to be the most promising next-generation antibiotics because of their broad-spectrum antimicrobial activities and minor side effects. Two new dermaseptin peptides, DMS-PS1 and DMS-PS2, have been identified by “shotgun” molecular cloning of encoding cDNAs in the crude skin secretions of the waxy monkey tree frog,Phyllomedusasauvagei. The mature peptide sequences predicted from the cloned cDNAs were separated from crude skin secretions and confirmed by mass spectrometry. Chemically synthetic replicates were assessed for various biological activities. Both dermaseptins were potently effective against a broad spectrum of microorganisms including antibiotic-resistant bacteria and displayed significant potency against gram-positive and gram-negative bacterial biofilms with low toxicity towards mammalian red blood cells. Remarkably, DMS-PS2 was effective against infections in murine skin caused by methicillin-resistantStaphylococcus aureusas a result of an induced wound. The actions of DMS-PS2 were with a membrane permeabilization mode. Overall, the data provided convincing evidence for the development of anti-infectious agents and/or biomaterials as a new therapeutic approach against bacterial infections.Statement of SignificanceBacterial adhesion to biomaterials remains a major problem. Antimicrobial peptides (AMPs) are well-known components of the innate immune system that can be applied to overcome biofilm-associated infections. Cationic dermaseptin peptides showed significant broad-spectrum antimicrobial activities and activities against bacterial biofilms of persistent infections in association with weak toxicity for mammalian red blood cells. The membrane permeabilizing ability of DMS-PS2 was confirmed, and importantly, it demonstrated potent efficiency of the treatment of MRSA infected murine skin model. Furthermore, beyond our expectation, DMS-PS2 showed a self-aggregating parameter, indicating a promising potential for the use of immobilized AMPs in clinical applications., which makes it also a promising suggestion for infection-proof biomaterial development.