Potential and use of bacterial small RNAs to combat drug resistance: a systematic review Hung Chan,1,* Jeffery Ho,1,* Xiaodong Liu,1 Lin Zhang,1–3 Sunny Hei Wong,2,4 Matthew TV Chan,1 William KK Wu1,2 1Department of Anesthesia and Intensive Care, 2State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, 3School of Biomedical Sciences, Faculty of Medicine, 4Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Shatin, Hong Kong *These authors contributed equally to this work 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. Keywords: antibiotic susceptibility, small RNAs, bacterial resistance, systematic reviews, antibacterial target