The Influence of sRNA on Gut Pathogen Drug Susceptibility

Researchers from the Helmholtz Institute for RNA-based Infection Research (HIRI) at Würzburg University and the University of California, Berkeley, USA, have made a significant breakthrough in understanding how gut bacteria adapt to their environment. They have identified a small ribonucleic acid (sRNA) that affects how the gut pathogen Bacteroides thetaiotaomicron responds to certain drugs. This discovery helps fill a major gap in our knowledge about the environmental adaptation of gut bacteria.

The results, published in Nature Microbiology, may provide the basis for innovative treatments targeting intestinal disorders and fighting antibiotic resistance.

The gut, a complex ecosystem comprising numerous microorganisms, is crucial to human well-being. Health can be impacted by variables that alter the microbiota, such as dietary modifications, drugs, or bile salts. Human gut bacteria that are commonly seen include Bacteroides thetaiotaomicron.

These intestinal microorganisms support human health by aiding in the digestion of polysaccharides. However, they can potentially encourage diseases in situations where the ecosystem is out of balance like following antibiotic treatment. Nevertheless, little is known about the molecular pathways that allow these intestinal microorganisms to adjust to their surroundings.

My group and I want to understand how Bacteroides thetaiotaomicron adapt to changing conditions in the gut.”

Alexander Westermann, Institute of Molecular Infection Biology, University of Würzburg

The research initiative is led by a group leader at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, which is part of the Braunschweig Helmholtz Centre for Infection Research (HZI), in collaboration with the Julius-Maximilians-Universität Würzburg (JMU).

Researchers from the University of California, Berkeley, USA, and HIRI experts worked together to map transcription units and characterize their expression under various experimental settings to shed light on the transcription networks in Bacteroides thetaiotaomicron.

The research team obtained a comprehensive understanding of the regulatory networks and the functional significance of sRNAs in bacterial adaptation by comparing this gene expression data with fitness data from genetically modified bacterial variations obtained from the literature.

Our findings offer new insights into the complex interplay between environmental cues, gene expression, and bacterial fitness.”

Alexander Westermann, Institute of Molecular Infection Biology, University of Würzburg

Small RNA Regulates Antibiotic Sensitivity

Through examining the nucleic acid composition of Bacteroides thetaiotaomicron, the scientists discovered a particular regulatory RNA molecule, known as a short RNA (sRNA), which affects the bacterium's susceptibility to antibiotics containing tetracycline.

With the discovery of the sRNA MasB and its role in modulating antibiotic sensitivity, we have revealed a previously uncharacterized regulatory mechanism,”

Daniel Ryan, Study First Author and Postdoctoral Researcher, Helmholtz Centre for Infection Research

The findings shed light on how members of the microbiota are affected by antibiotic treatments. This would allow for the development of fresh tactics to stop antibiotics from unintentionally harming helpful bacteria and advance treatments.

The results constitute a significant contribution to the microbiome community: the extensive transcriptome atlas, accessible to the general public via the web browser “Theta-Base,” offers the chance to examine additional sRNAs and investigate their roles in this context.

Westermann said, “The RNA biology of Bacteroides and other members of the gut microbiota is still poorly understood. Research endeavors of this kind lay the groundwork for future investigations, offering a foundational resource for further exploration.”

Source:
Journal reference:

Ryan, D., et al. (2024) An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity. Nature Microbiology. doi.org/10.1038/s41564-024-01642-9

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