1. Post-transcriptional control of the essential enzyme MurF by a small regulatory RNA in Brucella abortus.
- Author
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King KA, Benton AH, Caudill MT, Stoyanof ST, Kang L, Michalak P, Lahmers KK, Dunman PM, DeHart TG, Ahmad SS, Jutras BL, Poncin K, De Bolle X, and Caswell CC
- Subjects
- Animals, Mice, Brucella abortus metabolism, Gene Expression Regulation, Macrophages, Mice, Inbred BALB C, Proteomics, Brucellosis, RNA, Small Untranslated genetics, RNA, Small Untranslated metabolism
- Abstract
Brucella abortus is a facultative, intracellular, zoonotic pathogen that resides inside macrophages during infection. This is a specialized niche where B. abortus encounters various stresses as it navigates through the macrophage. In order to survive this harsh environment, B. abortus utilizes post-transcriptional regulation of gene expression through the use of small regulatory RNAs (sRNAs). Here, we characterize a Brucella sRNAs called MavR (for MurF- and virulence-regulating sRNA), and we demonstrate that MavR is required for the full virulence of B. abortus in macrophages and in a mouse model of chronic infection. Transcriptomic and proteomic studies revealed that a major regulatory target of MavR is MurF. MurF is an essential protein that catalyzes the final cytoplasmic step in peptidoglycan (PG) synthesis; however, we did not detect any differences in the amount or chemical composition of PG in the ΔmavR mutant. A 6-nucleotide regulatory seed region within MavR was identified, and mutation of this seed region resulted in dysregulation of MurF production, as well as significant attenuation of infection in a mouse model. Overall, the present study underscores the importance of sRNA regulation in the physiology and virulence of Brucella., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)
- Published
- 2024
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