Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction.

Gorm Mørk Hansen,Tim Tolker-Nielsen,Palle Holmstrup,Martin Nilsson,Claus Henrik Nielsen,Michael Givskov,Daniel Belstrøm,Peter Riis Hansen,Steffen Helqvist,Tom Coenye

doi:10.1371/journal.pone.0168771

Abstract

Chronic infection is associated with an increased risk of atherothrombotic disease and direct bacterial infection of arteries has been suggested to contribute to the development of unstable atherosclerotic plaques. In this study, we examined coronary thrombi obtained in vivo from patients with ST-segment elevation myocardial infarction (STEMI) for the presence of bacterial DNA and bacteria. Aspirated coronary thrombi from 22 patients with STEMI were collected during primary percutaneous coronary intervention and arterial blood control samples were drawn from radial or femoral artery sheaths. Analyses were performed using 16S polymerase chain reaction and with next-generation sequencing to determine bacterial taxonomic classification. In selected thrombi with the highest relative abundance of Pseudomonas aeruginosa DNA, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) with universal and species specific probes was performed to visualize bacteria within thrombi. From the taxonomic analysis we identified a total of 55 different bacterial species. DNA from Pseudomonas aeruginosa represented the only species that was significantly associated with either thrombi or blood and was >30 times more abundant in thrombi than in arterial blood (p<0.0001). Whole and intact bacteria present as biofilm microcolonies were detected in selected thrombi using universal and P. aeruginosa-specific PNA-FISH probes. P. aeruginosa and vascular biofilm infection in culprit lesions may play a role in STEMI, but causal relationships remain to be determined.

Highlights

Atherosclerosis (AS) is a chronic inflammatory disease, and vulnerable atherosclerotic plaques can rupture or erode, which can result in luminal thrombus formation and critical end-organ ischemia, e.g., stroke or myocardial infarction [1,2]
Coronary thrombi aspirated from patients with STsegment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) have been demonstrated to contain bacterial DNA [18, 19]
In this study we examined thrombi aspirated from culprit coronary lesions of patients with STEMI, and arterial blood control samples, with use of next-generation sequencing to determine the bacterial taxonomy, and PNA-FISH to investigate the presence of intact bacteria and bacterial biofilm

Summary

Introduction

Atherosclerosis (AS) is a chronic inflammatory disease, and vulnerable atherosclerotic plaques can rupture or erode, which can result in luminal thrombus formation and critical end-organ ischemia, e.g., stroke or myocardial infarction [1,2]. Biofilms are notoriously resistant to antibiotic treatment and host immune defenses, and can result in chronic infections including, for example, wound infections, middle ear infections, foreign body-associated infections, and periodontitis [16]. Coronary thrombi aspirated from patients with STsegment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) have been demonstrated to contain bacterial DNA [18, 19]. The aspirated material contains fragments from the lipid rich plaques of culprit coronary artery segments and PCI with thrombectomy can serve as a method of in vivo sampling of coronary thrombus and plaque material [20]. STEMI which is typically manifested by acute chest pain and characterized by STE in the patient’s electrocardiogram, is usually caused by acute thrombotic occlusion of a major coronary artery and (if untreated) is associated with considerable mortality and worsened long term prognosis

Methods

Results

Conclusion