The 3' UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions.

Mediati, DG; Dan, W; Lalaouna, D; Dinh, H; Pokhrel, A; Rowell, KN; Michie, KA; Stinear, TP; Cain, AK; Tree, JJ

The 3' UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions.

Mediati, DG Dan, W Lalaouna, D Dinh, H Pokhrel, A

Rowell, KN Michie, KA Stinear, TP Cain, AK Tree, JJ

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Publisher:: CELL PRESS
Publication Type:: Journal Article
Citation:: Cell Rep, 2024, 43, (4), pp. 114082
Issue Date:: 2024-04-23

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Field	Value	Language
dc.contributor.author	Mediati, DG
dc.contributor.author	Dan, W
dc.contributor.author	Lalaouna, D
dc.contributor.author	Dinh, H
dc.contributor.author	Pokhrel, A https://orcid.org/0000-0001-8897-2397
dc.contributor.author	Rowell, KN
dc.contributor.author	Michie, KA
dc.contributor.author	Stinear, TP
dc.contributor.author	Cain, AK
dc.contributor.author	Tree, JJ
dc.date.accessioned	2024-09-09T04:15:33Z
dc.date.available	2024-03-25
dc.date.available	2024-09-09T04:15:33Z
dc.date.issued	2024-04-23
dc.identifier.citation	Cell Rep, 2024, 43, (4), pp. 114082
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/180758
dc.description.abstract	Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S. aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using MS2-affinity purification coupled with RNA sequencing, we find that the vigR 3' UTR also regulates dapE, a succinyl-diaminopimelate desuccinylase required for lysine and peptidoglycan synthesis, suggesting a broader role in controlling cell wall metabolism and vancomycin tolerance. Deletion of the 3' UTR increased virulence, while the isaA mutant is completely attenuated in a wax moth larvae model. Sequence and structural analyses of vigR indicated that the 3' UTR has expanded through the acquisition of Staphylococcus aureus repeat insertions that contribute sequence for the isaA interaction seed and may functionalize the 3' UTR.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	CELL PRESS
dc.relation.ispartof	Cell Rep
dc.relation.isbasedon	10.1016/j.celrep.2024.114082
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.subject.classification	31 Biological sciences
dc.subject.mesh	Animals
dc.subject.mesh	3' Untranslated Regions
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Base Sequence
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Methicillin-Resistant Staphylococcus aureus
dc.subject.mesh	Moths
dc.subject.mesh	Staphylococcal Infections
dc.subject.mesh	Staphylococcus aureus
dc.subject.mesh	Vancomycin
dc.subject.mesh	Virulence
dc.subject.mesh	Animals
dc.subject.mesh	Moths
dc.subject.mesh	Staphylococcus aureus
dc.subject.mesh	Staphylococcal Infections
dc.subject.mesh	Vancomycin
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	3' Untranslated Regions
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Virulence
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Base Sequence
dc.subject.mesh	Methicillin-Resistant Staphylococcus aureus
dc.subject.mesh	Animals
dc.subject.mesh	3' Untranslated Regions
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Base Sequence
dc.subject.mesh	Gene Expression Regulation, Bacterial
dc.subject.mesh	Methicillin-Resistant Staphylococcus aureus
dc.subject.mesh	Moths
dc.subject.mesh	Staphylococcal Infections
dc.subject.mesh	Staphylococcus aureus
dc.subject.mesh	Vancomycin
dc.subject.mesh	Virulence
dc.title	The 3' UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions.
dc.type	Journal Article
utslib.citation.volume	43
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated	2024-09-09T04:15:31Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	43
utslib.citation.issue	4

Abstract:

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S. aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using MS2-affinity purification coupled with RNA sequencing, we find that the vigR 3' UTR also regulates dapE, a succinyl-diaminopimelate desuccinylase required for lysine and peptidoglycan synthesis, suggesting a broader role in controlling cell wall metabolism and vancomycin tolerance. Deletion of the 3' UTR increased virulence, while the isaA mutant is completely attenuated in a wax moth larvae model. Sequence and structural analyses of vigR indicated that the 3' UTR has expanded through the acquisition of Staphylococcus aureus repeat insertions that contribute sequence for the isaA interaction seed and may functionalize the 3' UTR.

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http://hdl.handle.net/10453/180758