Platelet activation and aggregation by the opportunistic pathogen Cutibacterium (Propionibacterium) acnes

Abstract

Cutibacterium (Propionibacterium) acnes, considered a part of the skin microbiota, is one of the most commonly isolated anaerobic bacteria from medical implants in contact with plasma. However, the precise interaction of C. acnes with blood cells and plasma proteins has not been fully elucidated. Herein, we have investigated the molecular interaction of C. acnes with platelets and plasma proteins. We report that the ability of C. acnes to aggregate platelets is dependent on phylotype, with a significantly lower ability amongst type IB isolates, and the interaction of specific donor-dependent plasma proteins (or concentrations thereof) with C. acnes. Pretreatment of C. acnes with plasma reduces the lag time before aggregation demonstrating that pre-deposition of plasma proteins on C. acnes is an important step in platelet aggregation. Using mass spectrometry we identified several plasma proteins deposited on C. acnes, including IgG, fibrinogen and complement factors. Inhibition of IgG, fibrinogen or complement decreased C. acnes-mediated platelet aggregation, demonstrating the importance of these plasma proteins for aggregation. The interaction of C. acnes and platelets was visualized using fluorescence microscopy, verifying the presence of IgG and fibrinogen as components of the aggregates, and co-localization of C. acnes and platelets in the aggregates. Here, we have demonstrated the ability of C. acnes to activate and aggregate platelets in a bacterium and donor-specific fashion, as well as added mechanistic insights into this interaction.

Regulation of Monospecies and Mixed Biofilms Formation of Skin Staphylococcus aureus and Cutibacterium acnes by Human Natriuretic Peptides

“…Cutibacterium acnes is one of predominant components of the skin microbiome (Petersson et al, 2018). It is suspected to be involved in acne formation, but its role remains unclear (Tomida et al, 2013).…”

“…Both S. aureus and C. acnes are opportunistic pathogens, and can sometimes be at the origin of skin disorders. In this way, C. acnes is considered to be one of the causes of acne vulgaris (Fitz-Gibbon et al, 2013; Achermann et al, 2014; Petersson et al, 2018). In parallel, it has been shown that C. acnes can be a cause of complications after operations and the setup of prosthetic implants (Howlin et al, 2017).…”

Cutibacterium acnes as an Opportunistic Pathogen: An Update of Its Virulence-Associated Factors

“…Like many other fibrinogen-binding proteins from Gram-positive bacteria, DsA1 may be involved in adaptive capacity, promoting the clumping action with fibrinogen and enabling the bacteria to colonize and tolerate the PSU environment [ 160 ]. Indeed, studies of plasma proteins have shown that fibrinogen adheres to the surface of C. acnes and mediates platelet aggregation [ 161 ]. DsA1 therefore appears to be an important surface protein expressed by C. acnes and further investigations of its role as a virulence factor are required.…”

Platelet plug formation in whole blood is enhanced in the presence of Porphyromonas gingivalis

“…When platelets were challenged with bacteria, a distinct lag phase preceded platelet aggregation (Kerrigan et al., 2007). This delay in aggregation was affected by the platelet to bacteria ratio, where increasing bacterial concentration reduced lag times (Petersson et al., 2018; Rasmussen et al., 2010). Bacterial interaction with platelets can occur via two main mechanisms: direct and indirect.…”