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一种针对鲍曼不动杆菌的新型烈性噬菌体属:在肺部感染小鼠模型中的疗效和安全性

A novel genus of virulent phage targeting Acinetobacter baumannii: Efficacy and safety in a murine model of pulmonary infection.

作者信息

Wang JiaWang, Hu Huan, Wang QingQing, Zhu TianZhu, Ren XiaoHan, Jiang WenQian, Hou XueMei, Lin Jun, Yu XiaoLing

机构信息

Department of Pharmacy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.

Institute of Applied Genomics, Fuzhou University, Fuzhou, China.

出版信息

PLoS Pathog. 2025 Jun 20;21(6):e1013268. doi: 10.1371/journal.ppat.1013268. eCollection 2025 Jun.

Abstract

Acinetobacter baumannii is a notable opportunistic pathogen responsible for severe hospital-acquired infections, with multidrug-resistant strains posing significant treatment challenges. Phage therapy, which employs bacteriophages as natural bacterial antagonists, has gained renewed attention as a promising solution to combat antibiotic-resistant infections. In this study, we isolated and characterized a novel virulent phage, vB_AbaS_qsb1, which specifically lyses A.baumannii. Phylogenetic and genomic analyses indicate that vB_AbaS_qsb1 is the founding member of a previously unreported genus, which we propose to name Acinibactriovirus, with Acinibactriovirus lysinus as the type species. vB_AbaS_qsb1 demonstrated robust stability across diverse temperature and pH ranges, a short latent period, and no known virulence or antibiotic resistance genes within its 54,713 bp dsDNA genome. Safety assessments showed that high-dose vB_AbaS_qsb1 induced no adverse effects in mice, with histopathology confirming its safety profile. Therapeutic experiments further indicated that vB_AbaS_qsb1 provided at least 50% protection against A.baumannii-induced pneumonia, significantly reducing bacterial loads and inflammation markers, while maintaining high phage titers in lung tissue.This study introduces vB_AbaS_qsb1 as a promising candidate for phage therapy against A.baumannii, offering both innovative insights and a valuable framework for future isolation, genomic characterization, and efficacy evaluation of phages targeting antibiotic-resistant bacteria.

摘要

鲍曼不动杆菌是一种引起严重医院获得性感染的重要机会致病菌,多重耐药菌株带来了重大的治疗挑战。噬菌体疗法利用噬菌体作为天然细菌拮抗剂,作为对抗抗生素耐药感染的一种有前景的解决方案,重新受到了关注。在本研究中,我们分离并鉴定了一种新型烈性噬菌体vB_AbaS_qsb1,它能特异性裂解鲍曼不动杆菌。系统发育和基因组分析表明,vB_AbaS_qsb1是一个此前未报道的属的首个成员,我们提议将其命名为不动杆菌病毒属,以溶不动杆菌病毒作为模式种。vB_AbaS_qsb1在不同温度和pH范围内表现出强大的稳定性,潜伏期短,在其54,713 bp的双链DNA基因组中没有已知的毒力或抗生素抗性基因。安全性评估表明,高剂量的vB_AbaS_qsb1对小鼠没有产生不良影响,组织病理学证实了其安全性。治疗实验进一步表明,vB_AbaS_qsb1对鲍曼不动杆菌引起的肺炎提供了至少50%的保护,显著降低了细菌载量和炎症标志物,同时在肺组织中保持了高噬菌体滴度。本研究将vB_AbaS_qsb1作为噬菌体疗法对抗鲍曼不动杆菌的一个有前景的候选者进行了介绍,为未来针对抗生素耐药细菌的噬菌体的分离、基因组表征和疗效评估提供了创新见解和有价值的框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/12208414/9320d2b122fc/ppat.1013268.g001.jpg

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