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The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2020 Sep 01; Vol. 222 (7), pp. 1188-1198. - Publication Year :
- 2020
-
Abstract
- Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are "susceptible" to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.<br /> (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Anti-Bacterial Agents therapeutic use
Bacteremia metabolism
Bacteremia microbiology
Biosynthetic Pathways
Disease Models, Animal
Endocarditis metabolism
Humans
Methicillin pharmacology
Rabbits
Endocarditis microbiology
Methicillin-Resistant Staphylococcus aureus pathogenicity
Purines biosynthesis
Staphylococcal Infections metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 222
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 32333768
- Full Text :
- https://doi.org/10.1093/infdis/jiaa202