RNA-Dependent Regulation of Virulence in Pathogenic Bacteria

Abstract

During infection, bacterial pathogens successfully sense, respond and adapt to a myriad of harsh environments presented by the mammalian host. This exquisite level of adaptation requires a robust modulation of their physiological and metabolic features. Additionally, virulence determinants, which include host invasion, colonization and survival despite the host's immune responses and antimicrobial therapy, must be optimally orchestrated by the pathogen at all times during infection. This can only be achieved by tight coordination of gene expression. A large body of evidence implicate the prolific roles played by bacterial regulatory RNAs in mediating gene expression both at the transcriptional and post-transcriptional levels. This review describes mechanistic and regulatory aspects of bacterial regulatory RNAs and highlights how these molecules increase virulence efficiency in human pathogens. As illustrative examples, Staphylococcus aureus, Listeria monocytogenes, the uropathogenic strain of Escherichia coli, Helicobacter pylori, and Pseudomonas aeruginosa have been selected.

Keywords: H. pylori; L. monocytogenes; P. aeruginosa; S. aureus; UPEC; regulatory RNA; riboregulation.

Figure 1

Schematic representation of major types of RNA-based regulatory mechanisms in pathogenic bacteria. (A) Riboswitches are most commonly part of the 5′UTR of the corresponding target mRNA. They are responsive to chemical ligands or environmental signals such as temperature (as in an RNA thermometer) for structural rearrangements leading to gene expression changes. sRNAs can be expressed from the complimentary strand (B) (as antisense RNA) or from a different genomic location (C). Blue: transcript under regulation; green: regulatory RNA. (D) Regulatory proteins (yellow) typically bind their target mRNAs (blue) at the RBS or the SD sequence to modulate their stability and/or activate/inhibit translation. Protein binding sRNAs (red) on the other hand can sequester these regulatory proteins by direct binding and titrate them away from their targetome. Pathogenic organisms not described in the main text are referred in this figure to highlight different RNAs as examples. For more details, refer to the following articles that have been extensively referred to for construction of this figure (Svensson and Sharma, ; Westermann, 2018).