VB_ST_E15 和 VB_ST_SPNIS2 这两种针对临床耐多药沙门氏菌血清型的微胶囊溶菌噬菌体的基因组特征、体外试验和临床前评估。

IF 4.6 2区 医学 Q1 MICROBIOLOGY
Reem A Youssef, Masarra M Sakr, Rania I Shebl, Bishoy T Saad, Khaled M Aboshanab
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引用次数: 0

摘要

背景:沙门氏菌感染仍然是威胁数百万人的重要公共卫生问题之一。随着对常规抗生素耐药性的增加,寻找替代品变得至关重要。在这项研究中,我们旨在分离、鉴定和评估两种针对临床分离的多重耐药(MDR)沙门氏菌血清型的噬菌体:方法:采用斑点试验筛选噬菌体的溶菌活性。通过确定宿主范围、寿命测试、温度、pH 值、有机溶剂的影响以及使用透射电子显微镜进行形态学表征,对分离出的噬菌体进行表征。基因组分析采用牛津纳米孔测序法进行。对游离噬菌体裂解物和微囊化配制噬菌体的体外和体内溶菌活性进行了评估:结果:成功分离出两种噬菌体(VB_ST_E15 和 VB_ST_SPNIS2),并显示出对 MDR 伤寒沙门氏菌(S. Typhimurium ATCC 14,028)、副伤寒沙门氏菌 A 和伤寒沙门氏菌的强溶菌活性。这两种噬菌体在测试温度下都能存活,感染力可维持 90 天,在 60 °C 温度下仍能保持活性,在 65 °C 温度下会发生热失活。它们在 pH 值为 3 到 11 的范围内具有溶菌能力,但在极酸或极碱的 pH 值下会失去活性。噬菌体可以耐受有机溶剂,但在 100%乙醇中会完全失活。这两种噬菌体都被归入 Caudoviricetes 目,Uetakevirus 属:Uetakevirus。这两种噬菌体的基因组序列均已组装、注释并提交至 NCBI GenBank 数据库(OR757455 和 OR757456)。使用小鼠动物模型进行的临床前评估显示,双噬菌体鸡尾酒可控制 MDR 沙门氏菌感染,细菌负荷的减少、动物体重的增加和组织病理学检查都证明了这一点:结论:这两种包裹噬菌体的配方可被视为治疗 MDR 沙门氏菌相关感染的理想候选药物,应进行临床分析以评估其在人类中的潜在用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic characterization, in vitro, and preclinical evaluation of two microencapsulated lytic phages VB_ST_E15 and VB_ST_SPNIS2 against clinical multidrug-resistant Salmonella serovars.

Background: Salmonella infections continue to be one of the essential public health issues threatening millions of people. With the increasing occurrence of resistance against conventionally used antibiotics, the search for alternatives has become crucial. In this study, we aimed to isolate, characterize, and evaluate two lytic bacteriophages against clinically isolated multidrug-resistant (MDR) Salmonella serovars.

Methods: Screening for the phage lytic activity was performed using a spot test. Characterization of the isolated phages was done by determining the host range, longevity test, and the effect of temperature, pH, organic solvents, and morphological characterization using a transmission electron microscope. Genomic analysis was performed using Oxford nanopore sequencing. The lytic activities of the free phage lysates and formulated phage as microencapsulated were evaluated both in vitro and in vivo.

Results: Two phages (VB_ST_E15 and VB_ST_SPNIS2) were successfully isolated and showed lytic strong activities against MDR Salmonella (S.) Typhimurium ATCC 14,028, S. Paratyphi A, and S. Typhi. The two phages survived at the tested temperatures, maintained their infectivity for 90 days, and retained their activity until 60 °C with thermal inactivation at 65 °C. They were lytic at a pH range from 3 to 11 but lost their activities at extremely acidic or alkaline pH. The phages could withstand the organic solvents but were completely inactivated by 100% ethanol. Both phages were classified under the order Caudoviricetes, and Genus: Uetakevirus. Their genomic sequences were assembled, annotated, and submitted to the NCBI GenBank database (OR757455 and OR757456). The preclinical evaluation using the murine animal model revealed that the two-phage cocktail managed MDR Salmonella infection as evidenced by the reduction in the bacterial burden, increased animal weight, and histopathological examination.

Conclusion: The two encapsulated phage formulas could be considered promising candidates for the management of MDR Salmonella-associated infections and clinical analysis should be undertaken to evaluate their potential use in humans.

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来源期刊
CiteScore
8.60
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.
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