The Staphylococcus aureus small non-coding RNA IsrR regulates TCA cycle activity and virulence.
Gustavo Rios-DelgadoAubrey K G McReynoldsEmma A PagellaJaviera NorambuenaPaul BriaudVincent ZhengMatthew J MunnekeJisun KimHugo RacineRonan CarrollEhud ZelzionEric SkaarJeffrey L BoseDane ParkerDavid LalaounaJeffrey M BoydPublished in: bioRxiv : the preprint server for biology (2024)
Staphylococcus aureus has evolved mechanisms to cope with low iron (Fe) availability in host tissues. S. aureus uses the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that an S. aureus Δ fur mutant has decreased expression of acnA , which codes for the Fe-dependent enzyme aconitase. Decreased acnA expression prevented the Δ fur mutant from growing with amino acids as sole carbon and energy sources. Suppressor analysis determined that a mutation in isrR , which produces a regulatory RNA, permitted growth by decreasing isrR transcription. The decreased AcnA activity of the Δ fur mutant was partially relieved by an Δ isrR mutation. Directed mutation of bases predicted to facilitate the interaction between the acnA transcript and IsrR, decreased the ability of IsrR to control acnA expression in vivo and IsrR bound to the acnA transcript in vitro . IsrR also bound to the transcripts coding the alternate TCA cycle proteins sdhC , mqo , citZ , and citM . Whole cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models.
Keyphrases
- staphylococcus aureus
- poor prognosis
- transcription factor
- metal organic framework
- gene expression
- aqueous solution
- biofilm formation
- escherichia coli
- binding protein
- single cell
- rna seq
- long non coding rna
- amino acid
- wild type
- liver failure
- respiratory failure
- cystic fibrosis
- drinking water
- cell therapy
- drug induced
- soft tissue
- heat shock