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新型孔蛋白Hol6A3在鲍曼不动杆菌噬菌体PD6A3中的表达及应用

Expression and application of a novel Holin Hol6A3 in phage PD6A3 of Acinetobacter baumannii.

作者信息

Wu Minle, Yang Yang, Wang Hanqing, Wang Beili, Pan Baishen, Xie Youhua, Guo Wei

机构信息

Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.

Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, 138 Medical College Road, Shanghai, 200032, China.

出版信息

BMC Microbiol. 2025 Jul 29;25(1):459. doi: 10.1186/s12866-025-04176-0.

Abstract

BACKGROUND

The current overuse of antibiotics presents significant challenges in treating drug-resistant bacterial infections. Bacteriophages have recently emerged as potential alternatives to antibiotics. Nevertheless, their high specificity and narrow host range limit their clinical application.

METHODS

The entire genome of phage PD6A3 was sequenced. Bioinformatic tools were employed to predict genes and determine protein structures. A prokaryotic expression system for Hol6A3 was established. The antibacterial efficacy, thermal and pH stability, and cytotoxicity of Hol6A3 were thoroughly investigated. Additionally, the in vitro antibacterial application of Holin was also studied.

RESULTS

This study achieved high-purity expression of Hol6A3, with a purity of 1.47 mg/ml. Biochemical properties revealed that Hol6A3 retained stable activity under various conditions. Hol6A3 exhibited broad-spectrum and potent bactericidal effects against various pathogens and synergistic effects in combating bacterial infections with endolysin Ply6A3.

CONCLUSION

Hol6A3 possesses considerable antibacterial potential, capable of degrading a broad spectrum of bacteria, demonstrating robust stability and a low propensity for the development of drug resistance. Consequently, Hol6A3 may emerge as a promising alternative to traditional antibiotics.

摘要

背景

目前抗生素的过度使用在治疗耐药细菌感染方面带来了重大挑战。噬菌体最近已成为抗生素的潜在替代品。然而,它们的高特异性和狭窄的宿主范围限制了其临床应用。

方法

对噬菌体PD6A3的全基因组进行测序。使用生物信息学工具预测基因并确定蛋白质结构。建立了Hol6A3的原核表达系统。对Hol6A3的抗菌效果、热稳定性和pH稳定性以及细胞毒性进行了深入研究。此外,还研究了溶菌酶在体外的抗菌应用。

结果

本研究实现了Hol6A3的高纯度表达,纯度为1.47毫克/毫升。生化特性表明,Hol6A3在各种条件下都保持稳定活性。Hol6A3对各种病原体表现出广谱且强效的杀菌作用,并且在与内溶素Ply6A3联合对抗细菌感染时具有协同作用。

结论

Hol6A3具有相当大的抗菌潜力,能够降解多种细菌,表现出强大的稳定性和较低的耐药性发展倾向。因此,Hol6A3可能成为传统抗生素的有前途的替代品。

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