PXD059048-1

PXD059048 is an original dataset announced via ProteomeXchange.

Title	Coupling tRNAGly gene redundancy with staphylococcal cell wall integrity, antibiotic susceptibility and virulence potential
Description	Redundancy in the number of tRNA genes which occur across species is poorly understood and, in many cases, remains essentially unexplored. In Staphylococcus aureus, several tRNAGly genes encode isoacceptors that either participate in protein synthesis or cell wall formation, upon aminoacylation by the sole glycyl-tRNA synthetase (GlyRS). Transcription of GlyRS, is regulated by a glyS T-box riboswitch in the 5’UTR, which responds to all tRNAGly isoacceptors and exhibits species-specific RNA conformations. To address whether disruption of the tRNAGly expression impacts the balance between ribosomal translation and cell wall formation, we used CRISPR/Cas9 editing to ablate one proteinogenic tRNAGly gene copy which is the stronger ligand of the glyS T-box riboswitch. Interestingly, no discernible impact on the growth and translational activity of S. aureus was observed, suggesting that the remaining tRNAs could make up for this deficiency. However, transcriptomics and proteomics analyses revealed that the edited strain had deficient cell wall integrity, and subsequent experimentation showed increased susceptibility to antibiotics targeting the cell wall. Interestingly, the observed alteration in the proteome level were independent of the glycine codon usage. Moreover, the edited strain exhibited reduced biofilm formation but retained its ability to invade human cell cultures. Overall, the present study highlights the important role of tRNA gene copy redundancy in the physiology of an important pathogen like S. aureus and consolidates the regulatory role of tRNAs in metabolic homeostasis.
HostingRepository	PRIDE
AnnounceDate	2025-07-21
AnnouncementXML	Submission_2025-07-20_16:41:57.989.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059048
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Johana Chicher
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-19 06:59:41	ID requested
⏵ 1	2025-07-20 16:41:58	announced

Kouvela A, Jaramillo Ponce JR, Giarimoglou N, Chicher J, Marzi S, Stathopoulos C, Stamatopoulou V, Coupling tRNAGly gene redundancy with staphylococcal cell wall integrity, antibiotic susceptibility, and virulence potential. Nucleic Acids Res, 53(13):(2025) [pubmed]

10.6019/PXD059048;

10.1093/nar/gkaf599;

submitter keyword: genome editing, tRNA-mediated metabolism regulation, Staphylococcus aureus,tRNA gene redundancy

Stefano Marzi
contact affiliation	Architecture et Réactivité de l'ARN, CNRS 9002, Université de Strasbourg, Strasbourg, France
contact email	s.marzi@ibmc-cnrs.unistra.fr
lab head
Johana Chicher
contact affiliation	Université de Strasbourg, Plateforme Protéomique Strasbourg-Esplanade, Centre National de la Recherche Scientifique
contact email	j.chicher@ibmc-cnrs.unistra.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059048
     1. Label: PRIDE project
     2. Name: Coupling tRNAGly gene redundancy with staphylococcal cell wall integrity, antibiotic susceptibility and virulence potential