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细菌小RNA对抗耐药性的潜力与应用:一项系统综述

Potential and use of bacterial small RNAs to combat drug resistance: a systematic review.

作者信息

Chan Hung, Ho Jeffery, Liu Xiaodong, Zhang Lin, Wong Sunny Hei, Chan Matthew Tv, Wu William Kk

机构信息

Department of Anesthesia and Intensive Care.

State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences.

出版信息

Infect Drug Resist. 2017 Dec 15;10:521-532. doi: 10.2147/IDR.S148444. eCollection 2017.

Abstract

BACKGROUND

Over the decades, new antibacterial agents have been developed in an attempt to combat drug resistance, but they remain unsuccessful. Recently, a novel class of bacterial gene expression regulators, bacterial small RNAs (sRNAs), has received increasing attention toward their involvement in antibiotic resistance. This systematic review aimed to discuss the potential of these small molecules as antibacterial drug targets.

METHODS

Two investigators performed a comprehensive search of MEDLINE, EmBase, and ISI Web of Knowledge from inception to October 2016, without restriction on language. We included all in vitro and in vivo studies investigating the role of bacterial sRNA in antibiotic resistance. Risk of bias of the included studies was assessed by a modified guideline of Systematic Review Center for Laboratory Animal Experimentation (SYRCLE).

RESULTS

Initial search yielded 432 articles. After exclusion of non-original articles, 20 were included in this review. Of these, all studies examined bacterial-type strains only. There were neither relevant in vivo nor clinical studies. The SYRCLE scores ranged from to 5 to 7, with an average of 5.9. This implies a moderate risk of bias. sRNAs influenced the antibiotics susceptibility through modulation of gene expression relevant to efflux pumps, cell wall synthesis, and membrane proteins.

CONCLUSION

Preclinical studies on bacterial-type strains suggest that modulation of sRNAs could enhance bacterial susceptibility to antibiotics. Further studies on clinical isolates and in vivo models are needed to elucidate the therapeutic value of sRNA modulation on treatment of multidrug-resistant bacterial infection.

摘要

背景

几十年来,人们一直在研发新型抗菌药物以对抗耐药性,但仍未成功。最近,一类新型的细菌基因表达调节剂——细菌小RNA(sRNA),因其与抗生素耐药性的关联而受到越来越多的关注。本系统评价旨在探讨这些小分子作为抗菌药物靶点的潜力。

方法

两名研究者对MEDLINE、EmBase和ISI Web of Knowledge数据库进行了全面检索,检索时间从建库至2016年10月,无语言限制。我们纳入了所有研究细菌sRNA在抗生素耐药性中作用的体外和体内研究。采用实验室动物实验系统评价中心(SYRCLE)的改良指南评估纳入研究的偏倚风险。

结果

初步检索得到432篇文章。排除非原创文章后,本评价纳入了20篇。其中,所有研究仅检测了细菌型菌株。既没有相关的体内研究,也没有临床研究。SYRCLE评分范围为5至7分,平均为5.9分。这意味着存在中度偏倚风险。sRNA通过调节与外排泵、细胞壁合成和膜蛋白相关的基因表达来影响抗生素敏感性。

结论

对细菌型菌株的临床前研究表明,调节sRNA可增强细菌对抗生素的敏感性。需要对临床分离株和体内模型进行进一步研究,以阐明sRNA调节在治疗多重耐药细菌感染中的治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed84/5736357/7bdf1b57f8d3/idr-10-521Fig1.jpg

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