Modulation of Bacterial Fitness and Virulence Through Antisense RNAs.

Jess A Millar,Rahul Raghavan

doi:10.3389/fcimb.2020.596277

Abstract

Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated asRNA, and asRNAs that require other RNAs or RNA-binding proteins for stability and activity. We explore how asRNAs improve bacterial fitness and virulence by modulating plasmid acquisition and maintenance, regulating transposon mobility, increasing resistance against bacteriophages, controlling flagellar production, and regulating nutrient acquisition. We conclude with a brief discussion on how this knowledge is helping to inform current efforts to develop new therapeutics.

Highlights

A major breakthrough in biology was the discovery of non-coding RNAs that regulate gene expression instead of coding for proteins. ncRNAs play important regulatory roles in all domains of life (Katayama et al, 2005; Beiter et al, 2009; Georg and Hess, 2011; Lybecker et al, 2014)
NcRNAs that are encoded on the opposite strands of target genes are known as cis-acting antisense RNAs, while an ncRNA that is encoded in a separate part of the genome in relation to its target messenger RNAs (mRNAs) is called a trans-acting small RNA (Waters and Storz, 2009; Thomason and Storz, 2010; Georg and Hess, 2011)
Their co-degradation along with target mRNAs allow precise control of regulatory circuits, which is key for bacteria to quickly adapt to host immune response (Storz et al, 2011; Updegrove et al, 2015). antisense RNAs (asRNAs) are useful for rapid gene regulation because they bind to target mRNAs with perfect complementarity, whereas small RNA (sRNA) form imperfect complementarity with target mRNAs and often require chaperone proteins such as Hfq and ProQ for stability and function (Georg and Hess, 2011; Saberi et al, 2016; Hoynes-O’Connor and Moon, 2016; Dutcher and Raghavan, 2018)

Summary

Introduction

A major breakthrough in biology was the discovery of non-coding RNAs (ncRNAs) that regulate gene expression instead of coding for proteins. ncRNAs play important regulatory roles in all domains of life (Katayama et al, 2005; Beiter et al, 2009; Georg and Hess, 2011; Lybecker et al, 2014). NcRNAs regulate gene expression at the post-transcriptional level by binding to messenger RNAs (mRNAs) to control several processes, including pathogenesis (Gripenland et al, 2010; Gottesman and Storz, 2011; Kacharia et al, 2017). AsRNAs have been shown to modulate bacterial pathogenicity by either regulating the expression of virulence genes (Giangrossi et al, 2010) or by controlling biochemical processes that improve bacterial fitness, which in turn boosts virulence (Gripenland et al, 2010; Lejars et al, 2019).

Results

Conclusion