Methicillin resistant Staphylococcus aureus adhesion to human umbilical vein endothelial cells demonstrates wall shear stress dependent behaviour

Abstract

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is an increasingly prevalent pathogen capable of causing severe vascular infections. The goal of this work was to investigate the role of shear stress in early adhesion events.MethodsHuman umbilical vein endothelial cells (HUVEC) were exposed to MRSA for 15-60 minutes and shear stresses of 0-1.2 Pa in a parallel plate flow chamber system. Confocal microscopy stacks were captured and analyzed to assess the number of MRSA. Flow chamber parameters were validated using micro-particle image velocimetry (PIV) and computational fluid dynamics modelling (CFD).ResultsUnder static conditions, MRSA adhered to, and were internalized by, more than 80% of HUVEC at 15 minutes, and almost 100% of the cells at 1 hour. At 30 minutes, there was no change in the percent HUVEC infected between static and low flow (0.24 Pa), but a 15% decrease was seen at 1.2 Pa. The average number of MRSA per HUVEC decreased 22% between static and 0.24 Pa, and 37% between 0.24 Pa and 1.2 Pa. However, when corrected for changes in bacterial concentration near the surface due to flow, bacteria per area was shown to increase at 0.24 Pa compared to static, with a subsequent decline at 1.2 Pa.ConclusionsThis study demonstrates that MRSA adhesion to endothelial cells is strongly influenced by flow conditions and time, and that MSRA adhere in greater numbers to regions of low shear stress. These areas are common in arterial bifurcations, locations also susceptible to generation of atherosclerosis.

Staphylococcus aureus-mediated blood-brain barrier injury: anin vitrohuman brain microvascular endothelial cell model

“…Interestingly, our findings also suggest that bacterial adhesion rates to both static and sheared endothelial cells (i.e., 0 and 10 dynes/cm 2 , respectively) are similar. This is consistent with a recent study by Viegas et al () who showed that adhesion rates of methicillin‐resistant SA (MRSA) to human umbilical vein endothelial cells (HUVECs) were relatively similar for static and normal shear conditions (when corrected for differences in bacterial concentration near the cell surface due to increasing shear level), but were considerably higher for low shear conditions. This led the authors to conclude that SA preferentially adheres to the vascular endothelium in vivo at atheroprone sites characterized by low or disturbed shear stress (Viegas et al, ).…”

Staphylococcus aureus adhesion in endovascular infections is controlled by the ArlRS–MgrA signaling cascade

“…Indeed, S . aureus adhesion to endothelium and endothelial ligands changes depending on the flow and shear stress [10, 30, 48–50]. In experiments where we mimicked conditions in the vasculature, the anti-adhesive effect of deletions in ArlRS–MgrA cascade become even more apparent than in static assays.…”

Pleural Empyema and Aortic Aneurysm

“…Mycoplasma pneumonia , a possible pathogen of PE, 30 , 31 is suspected to be associated with the development of subsequent AA because of cross-reactivity of the human heat shock protein with the immune response to bacterial antibodies 32 or because of increased adventitial inflammation, inhibition of TIMP-1 activity, and increased collagen degradation. 33 Methicillin-resistant Staphylococcus aureus (MRSA), a severe cause of empyema, was reported to be associated with atherosclerosis 34 ; thus, patients with MRSA-induced empyema may be at a higher risk of AA. There are 2 potential mechanisms of PE inducing IA.…”