In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratorygrown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes.A therosclerosis, or hardening of arteries, is one of the principal predisposing factors for heart attack and stroke in the United States, Europe, and Japan (1, 2). When atherosclerosis develops, the arterial walls thicken and lose elasticity due to the buildup of plaque deposits within the wall. Eventually, this condition may result in rupture of the overlying fibrous cap, which can lead to the development of a thrombosis or blood clot within the circulation (2). The progression of atherosclerosis is widely believed to be driven by increased levels of low-density lipoprotein (LDL) cholesterol in the blood (3), and this disease has been correlated with apolipoprotein E deficiency in mice (4). Over the past 20 years, research has shown that in addition to LDL/cholesterol, arterial plaque deposits typically contain infecting bacteria or signature prokaryotic biomarkers (2, 5-12). Previous work in our laboratory has shown that bacteria within carotid arterial plaques are present as biofilm infections and that at least one species of bacteria, Pseudomonas aeruginosa, which was commonly observed in the carotid arterial plaque samples we analyzed, undergoes a biofilm dispersion response when challenged in vitro with physiologically relevant levels of the catechol hormone norepinephrine in the presence of the iron chelator transferrin (13).In the present study, we analyzed atherosclerotic human carotid arteries for the presence of Propionibacterium acnes, a nonspore-forming, anaerobic, Gr...