RNA Chaperone Function in Bacterial Pathogenesis

Bacterial RNA chaperones, most prominently the Hfq protein, orchestrate post-transcriptional regulatory networks that underpin virulence, stress adaptation and host colonisation. By binding both small regulatory RNAs (sRNAs) and target mRNAs, Hfq accelerates RNA–RNA interactions, modulating mRNA stability and translational efficiency. This regulation shapes expression of toxins, adhesins, secretion systems and antibiotic‐resistance determinants. Beyond its canonical RNA-binding activity, Hfq can assemble into distinct higher-order structures and interact with cellular membranes, influencing biofilm formation, motility and intercellular communication. Exploiting these multifaceted roles, pathogens fine-tune gene expression in response to environmental cues, enhancing survival in hostile niches and during host invasion. A detailed understanding of RNA chaperone functions offers new avenues for antimicrobial intervention, including inhibitors that disrupt sRNA–mRNA pairing or block chaperone assembly.

Research from Nature Portfolio

Recent structural work has revealed that the intrinsically disordered C-terminal region of Hfq contains a minimal β-rich motif capable of forming amyloid-like filaments without perturbing the conserved Sm-like hexameric core. These filaments coexist with soluble hexamers in vivo and may act as a reserve pool, modulating the availability of active chaperone during stress or infection. Another study has unexpectedly demonstrated that Hfq interacts directly with bacterial inner membranes via its C-terminal amyloidogenic domain. Atomic force and cryo-electron microscopy showed that Hfq fibrils can disrupt lipid bilayers and promote the release of sRNA–protein complexes. This membrane-associated activity suggests a novel mechanism by which Hfq contributes to host-bacteria communication and sRNA export, expanding its functional repertoire beyond cytoplasmic RNA regulation.

RNA Chaperone Function in Bacterial Pathogenesis publication trend

The graph below shows the total number of articles in rna chaperone function in bacterial pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

RNA chaperone: A protein that facilitates the proper folding and interaction of RNA molecules without requiring ATP, stabilising transient RNA structures during gene regulation.

Hfq: A hexameric Sm-like RNA-binding protein in bacteria that promotes sRNA–mRNA pairing, affecting transcript stability and translation.

Small regulatory RNA (sRNA): Non-coding RNA molecules, typically 50–300 nucleotides long, that regulate gene expression by base-pairing with target mRNAs.

Outer membrane vesicle (OMV): Spherical lipid bilayer particles shed from the bacterial outer membrane that can transport proteins, lipids and nucleic acids to other cells.

Amyloid-like filament: A self-assembled, β-rich protein structure resembling amyloid fibrils, which can modulate protein function and localisation.

References

1. Hfq C-terminal region forms a β-rich amyloid-like motif without perturbing the N-terminal Sm-like structure. Communications Biology (2023).
2. Membrane association of the bacterial riboregulator Hfq and functional perspectives. Scientific Reports (2017).
3. Interactions and Insertion of Escherichia coli Hfq into Outer Membrane Vesicles as Revealed by Infrared and Orientated Circular Dichroism Spectroscopies. International Journal of Molecular Sciences (2023).
4. The RNA chaperone Hfq has a multifaceted role in Edwardsiella ictaluri. Frontiers in Cellular and Infection Microbiology (2024).
5. Impact of Hfq on Global Gene Expression and Virulence in Klebsiella pneumoniae. PLOS ONE (2011).