Characterization and bioinformatic analysis of a new chimeric endolysin against MRSA with great stability.

IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Sanaz Momen, Neda Soleimani, Farzaneh Azizmohseni, Yasaman Ahmadbeigi, Seddigheh Borhani, Zahra Amini-Bayat
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引用次数: 0

Abstract

Antibiotics become less effective in treating infectious diseases as resistance increases. Staphylococcus aureus is a global problem due to its ability to form biofilms and resistance mechanisms. Phage endolysin is one of the most promising methods for combating antibiotic resistance. ZAM-MSC chimeric endolysin has three domains derived from SAL1 and lysostaphin, which target the peptide bridge of peptidoglycan. In this study purified ZAM-MSC (with yield of 30 mg/lit) had bactericidal activity against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) at low concentrations (2.38 μg/ml and 1.88 μg/ml, respectively). The antibacterial spectrum revealed that ZAM-MSC was active against diverse Staphylococci. it has maintained 100% stability after 24 h incubation in pH 5 to 10 against S. aureus, as well as demonstrated significant thermostability and maintained nearly its full activity at different temperatures (4-42 °C) up to 1 day of incubation. The anti-biofilm activity of various concentrations of ZAM-MSC against MSSA and MRSA biofilms was not dose-dependent, and antibiofilm activity was observed even at low concentrations (14 μg/ml). Further, the molecular dynamics simulations demonstrated that the ZAM-MSC chimer and its parent proteins remained dynamically stable, showing similar flexibility despite the size and hydrogen bond number differences. In conclusion, the study reveals that chimeric ZAM-MSC is a distinctive enzyme with exceptional biochemical properties and rapid lytic activity against Staphylococci.

一种抗MRSA的新型嵌合内溶素的鉴定和生物信息学分析。
随着耐药性的增加,抗生素治疗传染病的效果越来越差。金黄色葡萄球菌是一个全球性的问题,由于其形成生物膜的能力和耐药机制。噬菌体内溶素是对抗抗生素耐药性最有前途的方法之一。ZAM-MSC嵌合型内溶素具有SAL1和溶葡萄蛋白衍生的三个结构域,靶向肽聚糖的肽桥。本研究纯化的ZAM-MSC(产率为30 mg/lit)在低浓度(分别为2.38 μg/ml和1.88 μg/ml)下对甲氧西林敏感金黄色葡萄球菌(MSSA)和耐甲氧西林金黄色葡萄球菌(MRSA)具有抑菌活性。抑菌谱显示,ZAM-MSC对多种葡萄球菌均有抑制作用。在pH为5 - 10的条件下对金黄色葡萄球菌孵育24小时后,它保持了100%的稳定性,并表现出明显的热稳定性,在不同温度(4-42°C)下孵育1天,几乎保持了其全部活性。不同浓度的ZAM-MSC对MSSA和MRSA生物膜的抗生物膜活性不存在剂量依赖性,即使在低浓度(14 μg/ml)下也能观察到抗生物膜活性。此外,分子动力学模拟表明,ZAM-MSC嵌合体及其亲本蛋白保持动态稳定,尽管大小和氢键数不同,但具有相似的柔韧性。综上所述,嵌合ZAM-MSC是一种独特的酶,具有特殊的生化特性和快速的裂解活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
AMB Express
AMB Express BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
2.70%
发文量
141
审稿时长
13 weeks
期刊介绍: AMB Express is a high quality journal that brings together research in the area of Applied and Industrial Microbiology with a particular interest in ''White Biotechnology'' and ''Red Biotechnology''. The emphasis is on processes employing microorganisms, eukaryotic cell cultures or enzymes for the biosynthesis, transformation and degradation of compounds. This includes fine and bulk chemicals, polymeric compounds and enzymes or other proteins. Downstream processes are also considered. Integrated processes combining biochemical and chemical processes are also published.
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