BR-bodies link RNA homeostasis to stress tolerance and intracellular fitness in Brucella
- 1Department of Biology, Indiana University
- 2Department of Microbiology, Genetics, and Immunology, Michigan State University
- 3Department of Biological Sciences, Wayne State University
Abstract
Bacterial gene expression depends on the coordinated regulation of RNA synthesis, processing, and decay. The conserved RNA degradosome scaffold, ribonuclease E (RNase E), assembles into phase-separated bacterial ribonucleoprotein bodies (BR-bodies) through its C-terminal intrinsically disordered region (IDR). This IDR also scaffolds recruitment of degradosome client proteins that carry out post-transcriptional gene regulation. Whether BR-bodies regulate virulence programs to support infection, however, is largely undefined. We show that RNase E of the intracellular pathogen Brucella ovis forms RNA-dependent condensates in vivo and phase-separates with RNA in vitro , with the IDR necessary and sufficient for BR-body assembly. Deleting the IDR [ rne (ΔIDR)] did not impair growth but sensitized Brucella to host-relevant oxidative and cell-envelope stressors. Transcriptome-wide profiling that simultaneously resolved mRNA decay and processing revealed that BR-bodies primarily accelerate mRNA turnover while stabilizing a distinct subset of transcripts. Notably, BR-bodies control the processing and levels of virB type IV secretion system mRNA and the turnover of its key activators, linking condensate-based RNA regulation to a core virulence pathway. Consistent with virB dysregulation, the rne (ΔIDR) mutant was severely attenuated in mammalian macrophages. To test whether phase separation is sufficient for BR-body function, we replaced the B. ovis IDR with the highly divergent Caulobacter crescentus IDR. This chimera assembled BR-bodies but rescued fitness incompletely, fully restoring oxidative-stress resistance but not cell-envelope stress resistance or intracellular fitness. BR-bodies therefore link RNA metabolism to Brucella stress resistance and infection, and their full function requires both phase separation and additional native IDR-specific activities, such as degradosome interactions.
IMPORTANCE: Biomolecular condensates are non-membrane-bound organelles that organize biological processes across all domains of life, but their role in bacterial infection is not well characterized. We show that Brucella , an intracellular bacterial pathogen and causative agent of the disease brucellosis, relies on biomolecular condensates called bacterial ribonucleoprotein bodies (BR-bodies) to control RNA stability and regulate gene expression. Without BR-bodies, Brucella is sensitized to host-relevant chemical stresses, cannot properly regulate essential infection machinery, and has severely diminished fitness within mammalian host cells. These results indicate that control of RNA levels by biomolecular condensates is required for Brucella survival within animal hosts, providing evidence that phase separation is a fundamental mechanism underlying Brucella adaptation to the hostile environment encountered during infection.
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BibTeX
@article{mallikaarachchi2026brbodies,
title = {{BR-bodies link RNA homeostasis to stress tolerance and intracellular fitness in Brucella}},
author = {Kaveendya S. Mallikaarachchi and Rosemary Northcote and Thomas Kim and Melene A. Alakavuklar and Vincent A. Lawal and Vidhyadhar Nandana and Aretha Fiebig and Jared M. Schrader and Sean Crosson},
journal = {mBio},
year = {2026},
month = oct,
doi = {10.1128/mbio.01705-26},
url = {https://journals.asm.org/doi/10.1128/mbio.01705-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - BR-bodies link RNA homeostasis to stress tolerance and intracellular fitness in Brucella
AU - Kaveendya S. Mallikaarachchi
AU - Rosemary Northcote
AU - Thomas Kim
AU - Melene A. Alakavuklar
AU - Vincent A. Lawal
AU - Vidhyadhar Nandana
AU - Aretha Fiebig
AU - Jared M. Schrader
AU - Sean Crosson
PY - 2026
DA - 2026/10/09
JO - mBio
DO - 10.1128/mbio.01705-26
UR - https://journals.asm.org/doi/10.1128/mbio.01705-26
AB - Bacterial gene expression depends on the coordinated regulation of RNA synthesis, processing, and decay. The conserved RNA degradosome scaffold, ribonuclease E (RNase E), assembles into phase-separated bacterial ribonucleoprotein bodies (BR-bodies) through its C-terminal intrinsically disordered region (IDR). This IDR also scaffolds recruitment of degradosome client proteins that carry out post-transcriptional gene regulation. Whether BR-bodies regulate virulence programs to support infection, however, is largely undefined. We show that RNase E of the intracellular pathogen Brucella ovis forms RNA-dependent condensates in vivo and phase-separates with RNA in vitro , with the IDR necessary and sufficient for BR-body assembly. Deleting the IDR [ rne (ΔIDR)] did not impair growth but sensitized Brucella to host-relevant oxidative and cell-envelope stressors. Transcriptome-wide profiling that simultaneously resolved mRNA decay and processing revealed that BR-bodies primarily accelerate mRNA turnover while stabilizing a distinct subset of transcripts. Notably, BR-bodies control the processing and levels of virB type IV secretion system mRNA and the turnover of its key activators, linking condensate-based RNA regulation to a core virulence pathway. Consistent with virB dysregulation, the rne (ΔIDR) mutant was severely attenuated in mammalian macrophages. To test whether phase separation is sufficient for BR-body function, we replaced the B. ovis IDR with the highly divergent Caulobacter crescentus IDR. This chimera assembled BR-bodies but rescued fitness incompletely, fully restoring oxidative-stress resistance but not cell-envelope stress resistance or intracellular fitness. BR-bodies therefore link RNA metabolism to Brucella stress resistance and infection, and their full function requires both phase separation and additional native IDR-specific activities, such as degradosome interactions. IMPORTANCE: Biomolecular condensates are non-membrane-bound organelles that organize biological processes across all domains of life, but their role in bacterial infection is not well characterized. We show that Brucella , an intracellular bacterial pathogen and causative agent of the disease brucellosis, relies on biomolecular condensates called bacterial ribonucleoprotein bodies (BR-bodies) to control RNA stability and regulate gene expression. Without BR-bodies, Brucella is sensitized to host-relevant chemical stresses, cannot properly regulate essential infection machinery, and has severely diminished fitness within mammalian host cells. These results indicate that control of RNA levels by biomolecular condensates is required for Brucella survival within animal hosts, providing evidence that phase separation is a fundamental mechanism underlying Brucella adaptation to the hostile environment encountered during infection.
SN - 2150-7511
ER -