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Updated: Aug 22, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction
Vance G Fowler1, George Sakoulas, Lauren M McIntyre
1Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA. vance.fowler@duke.edu
Background:
The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution.
Methods:
Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after > or =7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA.
Results:
The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; P=.0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4+/-14.8% vs. 11.6+/-6.5%, respectively; P=.005); (2) defective delta-lysin production (71.4% vs. 38.9%, respectively; P=.057); (3) non-agr genotype II profile (100% vs. 77.8%, respectively; P=.037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P=.015).
Conclusions:
Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.
Insights
Persistent bacteremia (PB) from methicillin-resistant Staphylococcus aureus (MRSA) is linked to specific bacterial traits. Isolates from PB patients showed higher in vitro survival, defective delta-lysin, non-agr genotype II, and a distinct PFGE type.
Area of Science:
- Infectious Diseases
- Microbiology
- Clinical Medicine
Background:
- Persistent bacteremia (PB) caused by methicillin-resistant Staphylococcus aureus (MRSA) has poorly understood origins.
- This study investigates associations between PB, clinical features, and bacterial characteristics in MRSA isolates.
Purpose of the Study:
- To identify in vitro bacterial genotypic and phenotypic characteristics associated with persistent bacteremia (PB) in MRSA infections.
- To compare these characteristics between MRSA isolates from patients with PB and those with resolving bacteremia (RB).
Main Methods:
- MRSA isolates from 21 PB patients and 18 RB patients were analyzed.
- Assessed characteristics included pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP) susceptibility, accessory gene regulator (agr) genotype and functionality (delta-lysin production), and autolysis phenotypes.
Main Results:
- Isolates from PB patients showed significantly higher in vitro survival after tPMP exposure (P=.005).
- PB isolates also exhibited higher rates of defective delta-lysin production (P=.057), non-agr genotype II (P=.037), and a specific PFGE genotype (P=.015) compared to RB isolates.
- Endocarditis was more frequent in PB patients (43%) than RB patients (0%) (P=.0016).
Conclusions:
- MRSA isolates from patients with persistent bacteremia exhibit distinct in vitro genotypic and phenotypic characteristics compared to those with resolving bacteremia.
- These bacterial factors may play a role in the development and persistence of MRSA bacteremia, warranting further investigation into their impact on clinical outcomes.
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