Isolation and characterization of a multidrug-resistant Staphylococcus aureus infecting phage and its therapeutic use in mice

IF 2.2 4区生物学 Q3 MICROBIOLOGY

Fems Microbiology Letters Pub Date : 2024-09-13 DOI:10.1093/femsle/fnae072

Zhen Xiao, Hongyi Xu, Juan Wang, Xueyuan Hu, Xiumei Huang, Shiping Song, Qingqing Zhang, Yanxin Liu, Yaopeng Liu, Na Liu, Junhui Liu, Ge Zhao, Xiyue Zhang, Yuehua Li, Jianmei Zhao, Junwei Wang, Huanqi Liu, Lin Wang, Zhina Qu

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引用次数: 0

Abstract

In recent years, the emergence of multidrug-resistant bacteria has limited the selection of drugs for treating bacterial infections, reduced clinical efficacy, and increased treatment costs and mortality. It is urgent to find alternative antibiotics. In order to explore a new method for controlling methicillin resistant Staphylococcus aureus (S. aureus) , this study isolated and purified a multi drug resistant S. aureus broad-spectrum phage JPL-50 from wastewater. JPL-50 belongs to the Siphoviridae family after morphological observation, biological characterization, and transmission electron microscopy (TEM) fragmentation spectrum analysis. It can cleave 84% of tested S. aureus (168/200) , in which 100% of tested mastitis-associated strains (48/48) and 72.04% of MRSA strains (67/93) were lysed. In addition, it has an optimal growth temperature of about 30°C, a high activity within a wide pH range (pH 3–10) , and an optimal multiplicity of infection of 0.01. The one-step growth curve shows a latent time of 20 minutes, an explosive time of 80 minutes. JPL-50 was 16, 927 bp in length and was encoded by double-stranded DNA, with no genes associated with bacterial resistance or virulence factors detected. In a therapeutic study, injection of the phage JPL-50 once and for 7 times in 7 days protected 40% and 60% of the mice from fatal S.aureus infection, respectively. More importantly, JPL-50-doxycycline combination could effectively inhibit host S.aureus in vitro and reduce the use of doxycycline within 8 hours. In conclusion, the bacteriophage JPL-50 has a wide lysis spectrum, high lysis rate, high tolerance to extreme environments, and moderate in vivo activity, providing ideas for developing multidrug-resistant S. aureus infections.

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耐多药金黄色葡萄球菌感染噬菌体的分离和特性鉴定及其在小鼠中的治疗用途

近年来，耐多药细菌的出现限制了治疗细菌感染药物的选择，降低了临床疗效，增加了治疗成本和死亡率。寻找替代抗生素迫在眉睫。为了探索一种控制耐甲氧西林金黄色葡萄球菌（S. aureus）的新方法，本研究从废水中分离并纯化了一种耐多药金黄色葡萄球菌广谱噬菌体 JPL-50。经过形态观察、生物学特性鉴定和透射电子显微镜（TEM）碎片谱分析，JPL-50属于Siphoviridae科。它能裂解 84% 的金黄色葡萄球菌（168/200），其中 100% 的乳腺炎相关菌株（48/48）和 72.04% 的 MRSA 菌株（67/93）被裂解。此外，它的最佳生长温度约为 30°C，在较宽的 pH 值范围（pH 值 3-10）内具有较高的活性，最佳感染倍数为 0.01。一步生长曲线显示潜伏时间为 20 分钟，爆发时间为 80 分钟。JPL-50 长度为 16,927 bp，由双链 DNA 编码，未检测到与细菌抗性或毒力因子相关的基因。在一项治疗研究中，注射噬菌体 JPL-50 一次和 7 天内注射 7 次，可分别保护 40% 和 60% 的小鼠免受致命金黄色葡萄球菌感染。更重要的是，JPL-50-多西环素组合能在体外有效抑制宿主金黄色葡萄球菌，并在 8 小时内减少多西环素的用量。总之，噬菌体JPL-50具有裂解谱广、裂解率高、对极端环境耐受性强、体内活性适中等特点，为开发耐多药金黄色葡萄球菌感染提供了思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fems Microbiology Letters 生物-微生物学

CiteScore

4.30

自引率

0.00%

发文量

112

审稿时长

1.9 months

期刊介绍： FEMS Microbiology Letters gives priority to concise papers that merit rapid publication by virtue of their originality, general interest and contribution to new developments in microbiology. All aspects of microbiology, including virology, are covered. 2019 Impact Factor: 1.987, Journal Citation Reports (Source Clarivate, 2020) Ranking: 98/135 (Microbiology) The journal is divided into eight Sections: Physiology and Biochemistry (including genetics, molecular biology and ‘omic’ studies) Food Microbiology (from food production and biotechnology to spoilage and food borne pathogens) Biotechnology and Synthetic Biology Pathogens and Pathogenicity (including medical, veterinary, plant and insect pathogens – particularly those relating to food security – with the exception of viruses) Environmental Microbiology (including ecophysiology, ecogenomics and meta-omic studies) Virology (viruses infecting any organism, including Bacteria and Archaea) Taxonomy and Systematics (for publication of novel taxa, taxonomic reclassifications and reviews of a taxonomic nature) Professional Development (including education, training, CPD, research assessment frameworks, research and publication metrics, best-practice, careers and history of microbiology) If you are unsure which Section is most appropriate for your manuscript, for example in the case of transdisciplinary studies, we recommend that you contact the Editor-In-Chief by email prior to submission. Our scope includes any type of microorganism - all members of the Bacteria and the Archaea and microbial members of the Eukarya (yeasts, filamentous fungi, microbial algae, protozoa, oomycetes, myxomycetes, etc.) as well as all viruses.