Abstract
The Gram-positive human pathogen Staphylococcus aureus is a leading cause of severe bacterial infections. Recent studies have shown that various cell types could readily internalize S. aureus and infected cells have been proposed to serve as vehicle for the systemic dissemination of the pathogen. Here we focused on the intracellular behavior of the Community-Associated Methicillin-Resistant S. aureus strain USA300. Supporting earlier observations, we found that wild-type S. aureus strain USA300 persisted for longer period within endothelial cells than within macrophages and that a mutant displaying the small colony variant phenotype (ΔhemDBL) had increased intracellular persistence. Time-lapse microscopy revealed that initial persistence of wild-type bacteria in endothelial cells corresponded to distinct single cell events, ranging from active intracellular bacterial proliferation, leading to cell lysis, to non-replicating bacterial persistence even 1 week after infection. In sharp contrast, ΔhemDBL mutant bacteria were essentially non-replicating up to 10 days after infection. These findings suggest that internalization of S. aureus in endothelial cells triggers its persistence and support the notion that endothelial cells might constitute an intracellular persistence niche responsible for reported relapse of infection after antibiotic therapy.
Highlights
The gram-positive bacterial pathogen, Staphylococcus aureus, can colonize multiple anatomic sites within its human host, including nares, respiratory tract and skin
Our aim was to follow the behavior of S. aureus USA300-LAC when internalized into endothelial cells and to understand how this fast growing extracellular pathogen may survive in the cytosol of these cells
Having confirmed the increased intracellular persistence of S. aureus USA300 in endothelial cells as compared to macrophages, we show here that the initial persistence of wild-type S. aureus in endothelial cells corresponds to distinct simultaneous situations at the single cell level
Summary
The gram-positive bacterial pathogen, Staphylococcus aureus, can colonize multiple anatomic sites within its human host, including nares, respiratory tract and skin. S. aureus is capable of systemic dissemination and can cause skin and soft tissue infections, pneumonia as well as sepsis, endocarditis, bones and joints infections (Thomer et al, 2016). The rates of infections caused by staphylococci, both community- and hospital-acquired strains, are regularly escalating (Laupland and Church, 2014). Treatment of these infections is becoming increasingly difficult due to the prevalence of multidrug-resistant strains. S. aureus USA300, an epidemic community-associated methicillin-resistant strain (CA-MRSA), has emerged as the predominant cause of methicillin-resistant S. aureus (MRSA) infections. Numerous cell types can ingest S. aureus and the bacterium is able to persist within these cells for quite variable periods of time (Fraunholz and Sinha, 2012; Strobel et al, 2016)
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