SWATH-MS-based proteomic analysis revealed the presence of periodontal bacterial proteins in ischemic stroke thrombi, with a predominance of Aggregatibacter actinomycetemcomitans.
Key Findings
Results
A total of 136 periodontal bacterial proteins were quantified in ischemic stroke thrombi, with the majority originating from Aggregatibacter actinomycetemcomitans.
136 total bacterial proteins were quantified across all samples
112 of the 136 proteins were from A. actinomycetemcomitans, representing the predominant species
The remaining proteins came from four other periodontal bacteria: Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, and Treponema denticola
Samples were obtained from nine severe periodontal patients with acute ischemic stroke during mechanical thrombectomy
Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and SWATH-MS quantitative proteomic profiling
Results
Sixteen bacterial proteins showed differential expression across stroke etiologies, predominantly from A. actinomycetemcomitans.
16 proteins were differentially expressed at p < 0.05
The differentially expressed proteins were mainly from A. actinomycetemcomitans
Three stroke subtypes were compared: large-artery atherosclerosis, cardioembolic, and undetermined source, with 3 patients per subtype
Differentially expressed proteins were further analyzed in silico to explore their functions and interactions
Results
Differentially expressed proteins from A. actinomycetemcomitans were primarily associated with transcription, translation, and stress response mechanisms, including oxidative stress resistance.
Functional categories of differentially expressed A. actinomycetemcomitans proteins included transcription, translation, and stress response
Oxidative stress resistance mechanisms were specifically identified among the differentially expressed protein functions
In silico analysis was used to characterize protein functions and interactions
Results
A collagenase from Tannerella forsythia was differentially expressed specifically in large-artery atherosclerosis stroke thrombi.
Few proteins from species other than A. actinomycetemcomitans were differentially expressed
Proteins from other species were mostly related to structural and basic metabolic functions
The T. forsythia collagenase was notably identified in large-artery atherosclerosis stroke thrombi, distinguishing it from other stroke subtypes
This finding was identified through SWATH-MS quantitative proteomic profiling with comparison across thrombus etiologies
Methods
The study design used thrombectomy-retrieved thrombi from patients with both severe periodontitis and acute ischemic stroke to enable direct proteomic characterization of bacterial content.
Nine patients were included, all with severe periodontal disease and acute ischemic stroke
Thrombotic samples were obtained during mechanical thrombectomy
Three stroke etiological subtypes were represented: large-artery atherosclerosis, cardioembolic, and undetermined source
The study focused on proteins from five periodontally relevant bacterial species: A. actinomycetemcomitans, P. gingivalis, F. nucleatum, T. forsythia, and T. denticola
SWATH-MS was selected for its ability to perform quantitative proteomic profiling
What This Means
This research suggests that bacteria commonly found in gum disease (periodontitis) leave detectable protein traces inside the blood clots that cause ischemic strokes. Scientists collected blood clots from nine patients who had both severe gum disease and acute ischemic stroke, retrieving the clots during a procedure called mechanical thrombectomy. Using advanced protein analysis technology, they identified 136 proteins from five types of periodontal bacteria within these clots, with the vast majority—112 proteins—coming from a single bacterium called Aggregatibacter actinomycetemcomitans.
The study also found that 16 of these bacterial proteins were expressed at different levels depending on what caused the stroke (large-artery disease, heart-related clots, or unknown causes). Many of these proteins were linked to bacterial survival functions such as responding to stress and resisting oxidative damage. Notably, an enzyme called collagenase from the bacterium Tannerella forsythia was found specifically in clots from strokes caused by large-artery disease, which is relevant because collagenase can break down tissue and potentially contribute to artery damage.
This research suggests a direct biological link between oral bacteria and the clots that cause strokes, supporting the idea that gum disease may not just be associated with stroke risk statistically, but that oral bacteria may physically contribute to clot formation or composition. The findings open questions about whether treating gum disease could influence stroke risk or clot characteristics, and they point to A. actinomycetemcomitans as a particularly important species to study further in the context of cardiovascular disease.