EOB-001: Synthetic RNA silencing in bacteria

Synthetic RNA silencing in bacteria – antimicrobial discovery and resistance breaking

Liam Good1 and James E. M. Stach2*

1 Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, UK
2 School of Biology, Newcastle University, Newcastle upon Tyne, UK

The increasing incidence and prevalence of antibiotic resistance in bacteria threatens the “antibiotic miracle.” Conventional antimicrobial drug development has failed to replace the armamentarium needed to combat this problem, and novel solutions are urgently required. Here we review both natural and synthetic RNA silencing and its potential to provide new antibacterials through improved target selection, evaluation, and screening. Furthermore, we focus on synthetic RNA silencers as a novel class of antibacterials and review their unique properties.

Front. Microbiol., 12 September 2011 | doi: 10.3389/fmicb.2011.00185

Figure 1
Figure 1. Natural RNA silencing in bacteria. (A) Antisense RNAs (asRNAs) that are cis-encoded share high degrees of complementarity with the target mRNA. (B) asRNAs that are trans-encoded have limited complementarity with the target mRNA and, in some species, require the an RNA chaperone (Hfq) to facilitate binding. In either case, once the asRNA is bound to the target mRNA, translation of the target gene (tarX) is silenced by inhibition of ribosome binding to the target mRNA (i); induced RNase degradation of the asRNA:mRNA hybrid (ii) or a combination of both processes.
Figure 2
Figure 2. Abundance and stability of antisense RNA is related to the efficacy of gene silencing. (A) Linear asRNAs are subject to degradation by RNases (i) and thus, are not available to form hybrids with their target mRNA. The role of Hfq in trans-encoded asRNAs with a high degree of sequence complementarity with the target mRNA is not elucidated, however, as with natural asRNAs, Hfq may serve to protect asRNAs from degradation (ii). In situations where the abundance and stability of the linear asRNA is low, only partial gene silencing will result (iii). (B) Addition of paired-termini to the asRNA results in asRNAs that have increased abundance, likely as a result of resistance to RNase degradation (iv). The role of Hfq in PTasRNA-mediated gene silencing is unclear. The increased abundance of PTasRNAs results in a higher level of gene silencing (v).

Reference

Good L and Stach JEM (2011) Synthetic RNA silencing in bacteria – antimicrobial discovery and resistance breaking. Front. Microbio. 2:185. doi: 10.3389/fmicb.2011.00185
URL: http://journal.frontiersin.org/article/10.3389/fmicb.2011.00185/full

Ming | 2015-03-26