A Novel Truncated CHAP Modular Endolysin, CHAPSAP26-161, That Lyses Staphylococcus aureus, Acinetobacter baumannii, and Clostridioides difficile, and Exhibits Therapeutic Effects in a Mouse Model of A. baumannii Infection.

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of microbiology and biotechnology Pub Date : 2024-08-28 Epub Date: 2024-06-17 DOI:10.4014/jmb.2402.02042
Yoon-Jung Choi, Shukho Kim, Ram Hari Dahal, Jungmin Kim
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Abstract

Development of novel antibacterial agents is imperative due to the increasing threat of antibiotic-resistant pathogens. This study aimed to develop the enhanced antibacterial activity and in-vivo efficacy of a novel truncated endolysin, CHAPSAP26-161, derived from the endolysin LysSAP26, against multidrug-resistant bacteria. CHAPSAP26-161 exhibited higher protein purification efficiency in E. coli and antibacterial activity than LysSAP26. Moreover, CHAPSAP26-161 showed the higher lytic activity against A. baumannii with minimal bactericidal concentrations (MBCs) of 5-10 μg/ml, followed by Staphylococcus aureus with MBCs of 10-25 μg/ml. Interestingly, CHAPSAP26-161 could lyse anaerobic bacteria, such as Clostridioides difficile, with MBCs of 25-50 μg/ml. At pH 4-8 and temperatures of 4°C-45°C, CHAPSAP26-161 maintained antibacterial activity without remarkable difference. The lytic activity of CHAPSAP26-161 was increased with Zn2+. In vivo tests demonstrated the therapeutic effects of CHAPSAP26-161 in murine systemic A. baumannii infection model. In conclusion, CHAPSAP26-161, a truncated endolysin that retains only the CHAP domain from LysSAP26, demonstrated enhanced protein purification efficiency and antibacterial activity compared to LysSAP26. It further displayed broad-spectrum antibacterial effects against S. aureus, A. baumannii, and C. difficile. Our in vitro and in-vivo results of CHAPSAP26-161 highlights its promise as an innovative therapeutic option against those bacteria with multiple antibiotic resistance.

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一种新型截短 CHAP 模块化内溶酶 CHAPSAP26-161,可溶解金黄色葡萄球菌、鲍曼不动杆菌和艰难梭菌,并在鲍曼不动杆菌感染小鼠模型中显示出治疗效果。
由于抗生素耐药性病原体的威胁日益严重,开发新型抗菌剂势在必行。本研究旨在开发一种新型截短内溶菌素 CHAPSAP26-161,该内溶菌素源自内溶菌素 LysSAP26,可增强其对耐多药细菌的抗菌活性和体内疗效。与 LysSAP26 相比,CHAPSAP26-161 在大肠杆菌中表现出更高的蛋白质纯化效率和抗菌活性。此外,CHAPSAP26-161 对鲍曼不动杆菌具有更高的杀菌活性,最小杀菌浓度为 5-10 μg/ml,其次是金黄色葡萄球菌,最小杀菌浓度为 10-25 μg/ml。有趣的是,CHAPSAP26-161 能裂解厌氧细菌,如艰难梭菌,其最大中浓度为 25-50 微克/毫升。在 pH 值为 4-8 和温度为 4oC-45oC 的条件下,CHAPSAP26-161 仍能保持抗菌活性,且无显著差异。CHAPSAP26-161 的溶菌活性随 Zn2+ 的增加而增强。体内试验证明了 CHAPSAP26-161 在小鼠全身鲍曼尼氏菌感染模型中的治疗效果。总之,CHAPSAP26-161 是一种仅保留了 LysSAP26 的 CHAP 结构域的截短内溶酶,与 LysSAP26 相比,它的蛋白质纯化效率和抗菌活性都有所提高。它还对金黄色葡萄球菌、鲍曼不动杆菌和艰难梭菌具有广谱抗菌作用。我们对 CHAPSAP26-161 的体外和体内研究结果表明,CHAPSAP26-161 有希望成为针对具有多重抗生素耐药性的细菌的创新治疗方案。
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来源期刊
Journal of microbiology and biotechnology
Journal of microbiology and biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-MICROBIOLOGY
CiteScore
5.50
自引率
3.60%
发文量
151
审稿时长
2 months
期刊介绍: The Journal of Microbiology and Biotechnology (JMB) is a monthly international journal devoted to the advancement and dissemination of scientific knowledge pertaining to microbiology, biotechnology, and related academic disciplines. It covers various scientific and technological aspects of Molecular and Cellular Microbiology, Environmental Microbiology and Biotechnology, Food Biotechnology, and Biotechnology and Bioengineering (subcategories are listed below). Launched in March 1991, the JMB is published by the Korean Society for Microbiology and Biotechnology (KMB) and distributed worldwide.
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