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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.

Titel:	Post-transcriptional control of the essential enzyme MurF by a small regulatory RNA in Brucella abortus.
Autor/in / Beteiligte Person:	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 ; Caswell, CC
Zeitschrift:	Molecular microbiology, Jg. 121 (2024), Heft 1, S. 129-141
Veröffentlichung:	Oxford, OX ; Boston, MA : Blackwell Scientific Publications, c1987-, 2024
Medientyp:	academicJournal
ISSN:	1365-2958 (electronic)
DOI:	10.1111/mmi.15207
Schlagwort:	Animals Mice Brucella abortus metabolism Gene Expression Regulation Macrophages Mice, Inbred BALB C Proteomics Brucellosis RNA, Small Untranslated genetics RNA, Small Untranslated metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Language: English [Mol Microbiol] 2024 Jan; Vol. 121 (1), pp. 129-141. <i>Date of Electronic Publication: </i>2023 Dec 11. MeSH Terms: Brucellosis* ; RNA, Small Untranslated* / genetics ; RNA, Small Untranslated* / metabolism ; Animals ; Mice ; Brucella abortus / metabolism ; Gene Expression Regulation ; Macrophages ; Mice, Inbred BALB C ; Proteomics References: Aronesty, E. (2013) Comparison of sequencing utility programs. The Open Bioinformatics Journal, 7, 1-8. ; Avila-Calderón, E.D., Flores-Romo, L., Witonsky, S., Donis-Maturano, L., Becerril-García, M.A., Arreola, M.G.A. et al. (2019) Dendritic cells and Brucella spp. interaction: the sentinel host and the stealthy pathogen. Folia Microbiologica, 65(1), 1-16. ; Barreteau, H., Kovac, A., Boniface, A., Sova, M., Gobec, S. & Blanot, D. 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Scientific Reports, 6, 25123. ; Zhou, J., Cai, Y., Liu, Y., An, H., Deng, K., Ashraf, M.A. et al. (2022) Breaking down the cell wall: still an attractive antibacterial strategy. Frontiers in Microbiology, 13, 952633. Grant Information: AI149124 National Institute of Allergy and Infectious Diseases; DMR-1933525 National Science Foundation Contributed Indexing: Keywords: Brucella abortus; small RNAs; virulence Substance Nomenclature: 0 (RNA, Small Untranslated) ; 0 (Rnf30 protein, mouse) Entry Date(s): Date Created: 20231212 Date Completed: 20240127 Latest Revision: 20240412 Update Code: 20240413

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Post-transcriptional control of the essential enzyme MurF by a small regulatory RNA in Brucella abortus.