Proteomic analysis of anti-MRSA activity of caerin 1.1/1.9 in a murine skin infection model and their in vitro anti-biofilm effects against Acinetobacter baumannii.

Proteomic analysis of anti-MRSA activity of caerin 1.1/1.9 in a murine skin infection model and their in vitro anti-biofilm effects against Acinetobacter baumannii.
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DOI:
10.1128/spectrum.04520-22
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发表时间:
2023-12-12
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
文献类型:
--
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Caerin 1是一个具有抗菌特性的宿主防御肽家族,最初从澳大利亚树蛙中分离出来。Caerin 1.1和Caerin 1.9都已被证明在体外和体内抑制由多种耐药性细菌引起的感染。在本研究中,我们比较了Caerin 1.1和Caerin 1.9(简称Caerin 1.1/1.9)与常用抗生素对各种细菌的最低抑菌浓度,包括金黄色葡萄球菌、铜绿假单胞菌、鲍曼不动杆菌和溶血性链球菌。我们的研究结果表明,caerin 1.1/1.9不仅可以阻止A.鲍曼不动杆菌,而且对已形成的生物膜也显示出治疗效果。此外,我们的研究表明,caerin 1.1/1.9显着抑制小鼠皮肤感染模型中耐甲氧西林金黄色葡萄球菌(MRSA)菌株的生长。作为我们研究的一部分进行的定量蛋白质组学分析表明,Caerin 1.1/1.9主要激活氧化磷酸化途径,沿着与组织修复和生长相关的几种途径。与感染耐甲氧西林金黄色葡萄球菌的未处理组织相比,观察到了这些发现。总之,我们的研究结果表明,caerin 1.1/1.9显示出作为治疗人类复杂耐药细菌感染的有希望的候选药物的潜力。Caerin 1.1和Caerin 1.9是从树蛙中提取的天然抗菌肽,已经证明能够抑制耐药细菌的生长,与某些广泛使用的抗生素相当。此外,这些肽表现出预防或治疗由细菌与身体成分结合形成的生物膜的能力。通过小鼠皮肤细菌感染模型,利用蛋白质组学分析作为技术方法,研究其抗菌作用的机制。
Caerin 1 is a family of host defense peptides with antimicrobial properties originally isolated from the Australian tree frog. Both caerin 1.1 and caerin 1.9 have been demonstrated to inhibit infections caused by multiple antibiotic-resistant bacteria, both in vitro and in vivo. In this current study, we conducted a comparison of the minimum inhibitory concentrations of caerin 1.1 and caerin 1.9 (referred to as caerin 1.1/1.9) with commonly used antibiotics against various bacteria, including Staphylococcus aureus, Copper-Green Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus haemolyticus. Our findings reveal that caerin 1.1/1.9 not only prevent the formation of biofilms by A. baumannii but also exhibit a therapeutic effect on established biofilms. Furthermore, our study demonstrates that caerin 1.1/1.9 significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) strains in a murine skin infection model. A quantitative proteomic analysis conducted as part of our study indicates that caerin 1.1/1.9 primarily activate oxidative phosphorylation pathways, along with several pathways associated with tissue repair and growth. These findings were observed in comparison to untreated tissues that were infected with MRSA in mice. In summary, our research outcomes suggest that caerin 1.1/1.9 exhibit the potential to serve as promising drug candidates for treating complicated antibiotic-resistant bacterial infections in humans. Caerin 1.1 and caerin 1.9, natural antimicrobial peptides derived from tree frogs, have demonstrated the ability to inhibit the growth of antibiotic-resistant bacteria, comparable to certain widely used antibiotics. Additionally, these peptides exhibit the capacity to prevent or treat biofilms formed by bacteria in conjunction with bodily components. The mechanisms underlying their antibacterial effects were investigated through a mouse model of bacterial skin infection, utilizing proteomic analysis as a technological approach.
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