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Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.
Freiberg, Jeffrey A; Reyes Ruiz, Valeria M; Gimza, Brittney D; Murdoch, Caitlin C; Green, Erin R; Curry, Jacob M; Cassat, James E; Skaar, Eric P.
Afiliación
  • Freiberg JA; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. jeffrey.freiberg@vumc.org.
  • Reyes Ruiz VM; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA. jeffrey.freiberg@vumc.org.
  • Gimza BD; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Murdoch CC; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Green ER; Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Curry JM; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cassat JE; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Skaar EP; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
Nat Commun ; 15(1): 6734, 2024 Aug 07.
Article en En | MEDLINE | ID: mdl-39112491
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.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Arginina / Infecciones Estafilocócicas / Staphylococcus aureus / Biopelículas / Antibacterianos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Arginina / Infecciones Estafilocócicas / Staphylococcus aureus / Biopelículas / Antibacterianos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos