Identification of a novel phage targeting methicillin-resistant Staphylococcus aureus In vitro and In vivo

Identification of a novel phage targeting methicillin-resistant Staphylococcus aureus In vitro and In vivo
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DOI:
10.1016/j.micpath.2020.104317
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发表时间:
2020-12-01
影响因子:
3.8
通讯作者:
He, Ping
He, Ping
中科院分区:
医学3区
文献类型:
--
作者:
Ji, Jiawei;Liu, Qian;He, Ping

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简介:金黄色葡萄球菌是一种常见的人类病原体,可引起多种疾病,包括皮肤、血液和下呼吸道的感染。耐甲氧西林金黄色葡萄球菌(MRSA)的出现使细菌感染的治疗变得更加困难,需要开发新的治疗方法。与传统的抗生素疗法相比,噬菌体疗法为对抗MRSA感染提供了一种有前景的选择。结果:我们从污水中分离的VBSAUS_SH-ST 15644噬菌体在体外和小鼠皮肤感染模型中对MRSA分离株具有抑制作用。噬菌体VB_SAUS_SH-ST 15644属于梭状病毒科。噬菌体基因组为45,111个碱基的双链DNA,GC含量为33.35%。在37株临床分离的MRSA中,有12株(32%)被噬菌体体外裂解。噬菌体在40℃或pH 6~9的温度范围内相对稳定,但对紫外光敏感。在4min内80%的噬菌体被吸附到宿主MRSA分离物上。一步生长曲线表明,潜伏期约为12min,其次为生长期(约9min)。据估计,每个感染细胞的突发性大小为13pfu。此外,在小鼠皮肤感染模型中,该噬菌体对MRSA感染有明显的抑制作用。结论:VBSAUS_SH-ST 15644噬菌体具有潜在的抑制MRSA皮肤感染的作用。
Introduction: Staphylococcus aureus is a common human pathogen that causes various diseases including infections on the skin, in the bloodstream and the lower respiratory tracts. The emergence of methicillin-resistant S. aureus (MRSA) made the treatment of the bacterial infection more difficult, calling for development of new therapeutics. Compared with conventional antibiotic therapy, phage therapy offers a promising alternative to combat infections caused by MRSA.Results: Here we showed that phage VB_SauS_SH-St 15644 isolated from sewage inhibited MRSA isolates in vitro and in the murine skin infection model. Phage VB_SauS_SH-St 15644 belongs to Siphoviridae. The genome of the phage is a linear, 45,111 bp double-stranded DNA with GC content of 33.35%. Among the 37 clinical MRSA isolates tested, 12 (32%) were lysed by the phage in vitro. The phage was relatively stable at temperatures up to 40 degrees C or between pH 6 and 9. However, the phage was sensitive to UV light. 80% of the phage was approximately adsorbed to the host MRSA isolate in 4 min. The one-step growth curve showed that the latent period was about 12 min followed by the growth period (about 9 min). The burst size was estimated at 13 PFU per infected cell. Furthermore, in a murine skin infection model, the phage significantly inhibited MRSA infection.Conclusions: Our study suggested that phage VB_SauS_SH-St 15644 has a potential to inhibit MRSA skin infection.