Role of Purine Biosynthesis in Persistent Methicillin-Resistant Staphylococcus aureus Infection
| Autor: | Liang Li, Kati Seidl, Niles P. Donegan, Arnold S. Bayer, Yu-Feng Zhou, Ambrose L. Cheung, Yan Q. Xiong, Michael R. Yeaman, Wessam Abdelhady |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | The Journal of Infectious Diseases. 218:1367-1377 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiy340 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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