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Role of Purine Biosynthesis in Persistent Methicillin-Resistant Staphylococcus aureus Infection.

  • Li L Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
  • Abdelhady W Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
  • Donegan NP Dartmouth Medical School, Hanover, New Hampshire.
  • Seidl K University Hospital of Zurich, Switzerland.
  • Cheung A Dartmouth Medical School, Hanover, New Hampshire.
  • Zhou YF Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
  • Yeaman MR Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
  • Bayer AS Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
  • Xiong YQ Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
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  • 2018-06-06
Published in:
  • The Journal of infectious diseases. - 2018
Animals
Anti-Bacterial Agents
Bacteremia
Disease Models, Animal
Humans
Methicillin
Methicillin-Resistant Staphylococcus aureus
Purines
Rabbits
Staphylococcal Infections
English 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/235937
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