The Staphylococcus aureus small non-coding RNA IsrR regulates TCA cycle activity and virulence.

Autor:	Rios-Delgado G; Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ, 08901, USA., McReynolds AKG; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kanas City, KS, 66103, USA., Pagella EA; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kanas City, KS, 66103, USA., Norambuena J; Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ, 08901, USA., Briaud P; Department of Biological Sciences, Ohio University, Athens, OH, 45701, USA., Zheng V; Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ, 08901, USA., Munneke MJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Kim J; Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, 07103, USA., Racine H; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, 67000, France., Carroll R; Department of Biological Sciences, Ohio University, Athens, OH, 45701, USA., Zelzion E; Office of Advanced Research Computing, Rutgers University, 96 Frelinghuysen Road Piscataway, NJ 08854, USA., Skaar E; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Bose JL; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kanas City, KS, 66103, USA., Parker D; Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, 07103, USA., Lalaouna D; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, 67000, France., Boyd JM; Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ, 08901, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 04. Date of Electronic Publication: 2024 Jul 04.
DOI:	10.1101/2024.07.03.601953
Abstrakt:	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.
Databáze:	MEDLINE
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