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天然噬菌体M8-2和M8-3对临床相关多重耐药菌的基因组洞察及裂解潜力

Genomic Insights into and Lytic Potential of Native Bacteriophages M8-2 and M8-3 Against Clinically Relevant Multidrug-Resistant .

作者信息

Rodríguez-Recio Francisco Ricardo, Garza-Cervantes Javier Alberto, Balderas-Cisneros Francisco de Jesús, Morones-Ramírez José Rubén

机构信息

Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León (UANL), San Nicolás de los Garza 66455, Mexico.

Centro de Investigación en Biotecnología y Nanotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Parque de Investigación e Innovación Tecnológica, Apodaca 66628, Mexico.

出版信息

Antibiotics (Basel). 2025 Jan 21;14(2):110. doi: 10.3390/antibiotics14020110.

DOI:10.3390/antibiotics14020110
PMID:40001355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11851605/
Abstract

Antibiotic resistance in pathogenic bacteria poses a critical global health threat, with multidrug-resistant (MDR) strains increasingly undermining conventional treatments. Among these, is a high-priority pathogen due to its resistance to carbapenems and frequent presence in hospital settings, contributing to severe healthcare-associated infections. This study aimed to isolate and characterize novel bacteriophages from environmental wastewater samples that could specifically target MDR . Two bacteriophages, M8-2 and M8-3, were isolated from wastewater in Monterrey, Mexico. A genomic analysis classified M8-2 and M8-3 within the family, and next-generation sequencing (NGS) was used to confirm the absence of undesirable antibiotic resistance or virulence genes. Optimization of viral amplification was performed to achieve high titers, with structural proteins characterized by SDS-PAGE. Phages M8-2 and M8-3 exhibited specific lytic activity against MDR strains of , offering a targeted approach to combat antibiotic-resistant infections. High genetic similarity (>95%) to known Gram-negative bacterial phages was observed. Optimized viral amplification yielded titers of 4.2 × 10 and 1.03 × 10 PFUs/mL for M8-2 and M8-3, respectively. The specificity of these phages minimized disruption to the host microbiome, and their significant efficacy in suppressing bacterial growth positions bacteriophages as promising candidates for localized and personalized phage therapy, especially in chronic and hospital-acquired infection settings. These findings highlight the therapeutic potential of M8-2 and M8-3 in addressing antibiotic-resistant infections. Their safety profile, high target specificity, and robust lytic activity underscore the feasibility of incorporating phage-based strategies into current antimicrobial protocols. This study contributes to the broader goal of developing sustainable and effective phage therapies for diverse clinical and environmental contexts.

摘要

病原菌中的抗生素耐药性对全球健康构成了严重威胁,多重耐药(MDR)菌株日益破坏传统治疗方法。其中,由于其对碳青霉烯类药物的耐药性以及在医院环境中的频繁出现,导致严重的医疗相关感染,因此是一种高优先级病原体。本研究旨在从环境废水样本中分离和鉴定能够特异性靶向MDR的新型噬菌体。从墨西哥蒙特雷的废水中分离出两种噬菌体,M8 - 2和M8 - 3。基因组分析将M8 - 2和M8 - 3归类为 科,采用下一代测序(NGS)来确认不存在不良抗生素耐药性或毒力基因。进行了病毒扩增优化以获得高滴度,通过SDS - PAGE对结构蛋白进行了表征。噬菌体M8 - 2和M8 - 3对MDR菌株表现出特异性裂解活性,为对抗抗生素耐药性感染提供了一种靶向方法。观察到与已知革兰氏阴性细菌噬菌体具有高度遗传相似性(>95%)。优化后的病毒扩增分别使M8 - 2和M8 - 3的滴度达到4.2×10 和1.03×10 PFU/mL。这些噬菌体的特异性使对宿主微生物群的破坏最小化,它们在抑制细菌生长方面的显著功效使噬菌体成为局部和个性化噬菌体治疗的有希望的候选者,特别是在慢性和医院获得性感染环境中。这些发现突出了M8 - 2和M8 - 3在解决抗生素耐药性 感染方面的治疗潜力。它们的安全性、高靶向特异性和强大的裂解活性强调了将基于噬菌体的策略纳入当前抗菌方案的可行性。本研究有助于实现为不同临床和环境背景开发可持续和有效噬菌体疗法这一更广泛的目标。

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本文引用的文献

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Bacteriophage self-counting in the presence of viral replication.病毒复制情况下的噬菌体自我计数
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Specific Integration of Temperate Phage Decreases the Pathogenicity of Host Bacteria.温和噬菌体的特异性整合降低了宿主细菌的致病性。
Front Cell Infect Microbiol. 2020 Feb 4;10:14. doi: 10.3389/fcimb.2020.00014. eCollection 2020.
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PA5oct Jumbo Phage Impacts Planktonic and Biofilm Population and Reduces Its Host Virulence.PA5oct 巨型噬菌体影响浮游生物和生物膜种群并降低其宿主毒力。
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The environmental occurrence of Pseudomonas aeruginosa.铜绿假单胞菌的环境发生情况。
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Phages for Phage Therapy: Isolation, Characterization, and Host Range Breadth.用于噬菌体疗法的噬菌体:分离、表征及宿主范围广度
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Bacteriophage Therapy Increases Complement-Mediated Lysis of Bacteria and Enhances Bacterial Clearance After Acute Lung Infection With Multidrug-Resistant Pseudomonas aeruginosa.噬菌体治疗增强补体介导的细菌溶解作用,并在多重耐药铜绿假单胞菌引起的急性肺部感染后增强细菌清除。
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Prevention of Dermal Abscess Formation Caused by Using Phage JD007 in Nude Mice.在裸鼠中使用噬菌体JD007预防皮肤脓肿形成
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