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Role of Purine Biosynthesis in Persistent Methicillin-Resistant Staphylococcus aureus Infection
- Source :
- The Journal of Infectious Diseases. 218:1367-1377
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus endovascular infections. In this study, we investigated potential genetic mechanisms underlying the persistent outcomes. Compared with resolving bacteremia (RB) isolates (defined as isolates associated with negative results of blood cultures 2–4 days after initiation of therapy), PB strains (defined as isolates associated with positive results of blood cultures ≥7 days after initiation of therapy) had significantly earlier onset activation of key virulence regulons and structural genes (eg, sigB, sarA, sae, and cap5), higher expression of purine biosynthesis genes (eg, purF), and faster growth rates, with earlier entrance into stationary phase. Importantly, an isogenic strain set featuring a wild-type MRSA isolate, a purF mutant strain, and a purF-complemented strain and use of strategic purine biosynthesis inhibitors implicated a causal relationship between purine biosynthesis and the in vivo persistent outcomes. These observations suggest that purine biosynthesis plays a key role in the outcome of PB and may represent a new target for enhanced efficacy in treating life-threatening MRSA infections.
- Subjects :
- Methicillin-Resistant Staphylococcus aureus
0301 basic medicine
Meticillin
medicine.drug_class
030106 microbiology
Antibiotics
Virulence
Bacteremia
Biology
medicine.disease_cause
Microbiology
Methicillin
Major Articles and Brief Reports
03 medical and health sciences
medicine
Animals
Humans
Immunology and Allergy
Purine metabolism
Structural gene
Staphylococcal Infections
medicine.disease
Methicillin-resistant Staphylococcus aureus
Anti-Bacterial Agents
Disease Models, Animal
030104 developmental biology
Infectious Diseases
Purines
Staphylococcus aureus
Rabbits
medicine.drug
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 218
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....398b0900f1eb2a238249d642a42eb307