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

• Published in: Infection and drug resistance 2017-01, Vol.10, p.521-532
• Main Authors: Chan, Hung, Ho, Jeffery, Liu, Xiaodong, Zhang, Lin, Wong, Sunny Hei, Chan, Matthew Tv, Wu, William Kk
• Format: Article
• Language: English
• Subjects: Analysis; Animal research; Antibacterial agents; Antibiotic resistance; antibiotic susceptibility; Antibiotics; Bacteria; Bacterial infections; bacterial resistance; Bias; Bibliographic data bases; Cell walls; Clinical isolates; Drug resistance; E coli; Enzymes; Gene expression; Gene loci; Genetic aspects; Laboratory animals; Membrane proteins; Microbial drug resistance; Mortality; Multidrug resistance; Polymerase chain reaction; Proteins; Review; Reviews; RNA; Search engines; small RNAs; Strains (organisms); Systematic review; Trends
• ISSN: 1178-6973; 1178-6973
• DOI: 10.2147/IDR.S148444

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. 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). 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. 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.