Abstract

BackgroundThe interaction between pathogenic bacteria and cholesterol crystals (CCs) has not been investigated. However, CCs are found extensively in atherosclerotic plaques and sclerotic cardiac valves. Interactions between pathogenic bacteria and CCs could provide insights into destabilization of atherosclerotic plaques and bacterial adhesion to cardiac valves.MethodsStaphylococcus aureus and Pseudomonas aeruginosa were used to assess in vitro bacterial adhesion to CCs and proliferation in the presence of CCs compared to plastic microspheres and glass shards as controls. Ex vivo studies evaluated bacterial adhesion to atherosclerotic rabbit arteries compared to normal arteries and human atherosclerotic carotid plaques compared to normal carotid arteries. Scanning electron microscopy (SEM) was used to visualize bacterial adhesion to CCs and confocal microscopy was used to detect cholesterol binding to bacteria grown in the presence or absence of CCs.ResultsIn vitro, S. aureus and P. aeruginosa displayed significantly greater adhesion, 36% (p<0.0001) and 89% (p<0.0001), respectively, and growth upon exposure to CCs compared to microspheres or glass shards. Rabbit and human atherosclerotic arteries contained significantly greater bacterial burdens compared to controls (4× (p<0.0004); 3× (p<0.019), respectively. SEM demonstrated that bacteria adhered and appeared to degrade CCs. Consistent with this, confocal microscopy indicated increased cholesterol bound to the bacterial cells.ConclusionsThis study is the first to demonstrate an interaction between bacteria and CCs showing that bacteria dissolve and bind to CCs. This interaction helps to elucidate adhesion of bacteria to sclerotic valves and atherosclerotic plaques that may contribute to endocarditis and plaque destabilization.

Highlights

  • Bacteria residing in atherosclerotic plaques has been reported but their role in atherosclerosis has been unclear

  • S. aureus and P. aeruginosa displayed significantly greater adhesion, 36% (p

  • Scanning electron microscopy (SEM) demonstrated that bacteria adhered and appeared to degrade CCs

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Summary

Introduction

Bacteria residing in atherosclerotic plaques has been reported but their role in atherosclerosis has been unclear. Despite evidence implying a bacterial-plaque interaction, inflammation triggered by cholesterol crystals (CCs) in the absence of detectable bacteria promotes atherosclerosis further complicating a clear connection between bacterial colonization and arterial blockage [2, 3]. We previously discovered that as cholesterol undergoes a phase change from a liquid to a crystalline state it occupies a greater volume. This can cause volume expansion within the lipid core leading to perforation of the fibrous cap and destabilization of the atherosclerotic plaque [7, 8]. In human coronary arteries during myocardial infarction scavenger cells, primarily macrophages were present engulfing, degrading, and binding to CCs [11]. Interactions between pathogenic bacteria and CCs could provide insights into destabilization of atherosclerotic plaques and bacterial adhesion to cardiac valves

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