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| Status |
Public on Jul 10, 2024 |
| Title |
Restriction of Arginine Induces Antibiotic Tolerance in Staphylococcus aureus |
| Organism |
Staphylococcus aureus |
| Experiment type |
Other
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| Summary |
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 were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to 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 was found to induce antibiotic tolerance via inhibition of protein synthesis. In a mouse skin infection model, 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.
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| Overall design |
This study performed a genome wide TnSeq screen comparing S. aureus grown as a filter colony biofilm for 48 hours and exposed to 5 different conditions (no antibiotics or 4 different antibiotics) for another 48 hours. S. aureus grown as a biofilm for 48 or 96 hours was also compared to the input
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| Contributor(s) |
Freiberg JA, Ruiz VM, Gimza BD, Murdoch CC, Green ER, Curry JM, Cassat JE, Skaar EP |
| Citation(s) |
39112491 |
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| Submission date |
May 15, 2024 |
| Last update date |
Sep 03, 2024 |
| Contact name |
Eric P Skaar |
| Organization name |
Vanderbilt University Medical Center
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| Street address |
1161 21st Avenue South, A5303B MCN
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| City |
Nashville |
| State/province |
Tennessee |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (1) |
| GPL19006 |
Illumina HiSeq 2500 (Staphylococcus aureus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA1112082 |
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