Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus

Jeffrey A. Freiberg (), Valeria M. Reyes Ruiz, Brittney D. Gimza, Caitlin C. Murdoch, Erin R. Green, Jacob M. Curry, James E. Cassat and Eric P. Skaar ()
Additional contact information
Jeffrey A. Freiberg: Vanderbilt University Medical Center
Valeria M. Reyes Ruiz: Vanderbilt University Medical Center
Brittney D. Gimza: Vanderbilt University Medical Center
Caitlin C. Murdoch: Vanderbilt University Medical Center
Erin R. Green: Vanderbilt University Medical Center
Jacob M. Curry: Vanderbilt University Medical Center
James E. Cassat: Vanderbilt University Medical Center
Eric P. Skaar: Vanderbilt University Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics are examined using both quantitative proteomics and transposon sequencing. These screens indicate that arginine metabolism is involved in antibiotic tolerance within a biofilm and support the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction induces antibiotic tolerance via inhibition of protein synthesis. In murine skin and bone infection models, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51144-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51144-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51144-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().