Role of Purine Biosynthesis in Persistent Methicillin-Resistant Staphylococcus aureus Infection
Year: 2018
Type: article
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.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Mitigating Resistance & Virulence in MRSA, The role of GraRS in resistance to cationic antimicrobial peptides in S. aureus, Mitigating Resistance & Virulence in MRSA, Mechanisms of Staphylococcal Co-Resistance to Daptomycin and Host Defense Peptide, Early agr Activation is a Key Pathogenic Signature in Persistent MRSA Bacteremia, Systems Immunolobiology of Antibiotic-Persistent MRSA Infection, G9000111704
OpenAlex ID: W2807673815