Staphylococcus aureus Endocarditis Immunothrombosis

Abstract

Background: Infective endocarditis continues to represent a challenge for healthcare systems, requiring careful management and resources. Recent studies have indicated a shift in the predominant pathogens of concern, with Streptococcus sp. a being superseded by Staphylococcus sp. and Enterococcus sp. as the leading causes of concern. This shift is of concern as it is associated with Staphylococcus Aureus which has a high virulence rate and a tendency to form a biofilm, meaning that non-surgical therapy may not be effective. It is imperative to deliberate on the likelihood of platelet blood clot formation, which may be accompanied by bacterial infestation and the development of a biofilm. Methods: MEDLINE, Embase, and Pubmed were searched using terms relating to 'endocarditis' and 'Staphilococcus aureus', along with 'epidemiology', 'pathogenesis', 'coagulation', 'platelet', 'aggregation', and 'immunity'. The search focused on publications from the past 15 years, but excluded older, highly regarded articles. We also searched the reference lists of relevant articles. Recommended review articles are cited for more details. Results: An endocarditis lesion is believed to be a blood clot infected with bacteria that adheres to the heart valves. Infective endocarditis is a good example of immunothrombosis, where the coagulation system, innate immunity and the function of coagulation in isolating and eliminating pathogens interact. However, in the context of infective endocarditis, immunothrombosis unintentionally establishes an environment conducive to bacterial proliferation. The process of immunothrombosis impedes the immune system, enabling bacterial proliferation. The coagulation system plays a pivotal role in the progression of this condition. Conclusion: The coagulation system is key to how bacteria attach to the heart valves, how vegetations develop, and how complications like embolisation and valve dysfunction occur. Staphylococcus aureus, the main cause of infective endocarditis, can change blood clotting, growing well in the fibrin-rich environment of vegetation. The coagulation system is a good target for treating infective endocarditis because of its central role in the disease. But we must be careful, as using blood-thinning medicines in patients with endocarditis can often lead to an increased risk of bleeding.

Keywords: Staphylococcus aureus; Staphylococcus aureus infection; immunoresponse; infective endocarditis; platelet activation; thromboimmunity.

Figure 1

The prevalence of IE has been observed to occur most frequently among the elderly with a history of CIEDs, as well as among younger individuals with a history of IDVU. Conversely, a lower incidence has been documented in patients with central venous catheters, HIV, CHD, and those experiencing immunosuppression. * Low numbers of Coxiella burnetii, Bartonella quintana, Pseudomonas aeruginosa, Tropheryma whipplei, Enterobacteriaceae, Acinetobacter ursingii, Listeria monocytogenes, Propionibacterium acnes, Lactobacillus spp., Corynebacterium spp., Francisella tularensis, Erysipelothrix rhusiopathiae, Gordonia bronchialis, Bacillus spp., Catabacter hongkongensi, Moraxella catarrhalis, Campylobacter foetus, Neisseria elongata and Veillonella spp. Abbreviations: CIED, cardiac implantable electronic devices; CHD, congenital heart disease; CoNS, coagulase negative; HIV, immunodeficiency virus; IDVU, intravenous drug user; IE, infective endocarditis. * This information has been derived from the work of Selton-Suty C et al. Clin Infect Dis 2012; 54: 1230–39. Ref. [15]. Figure from Nappi et al. Ref. [15].

Figure 2

The illustration depicts the prevalence of healthcare-associated infections in developing countries according to the World Health Organisation (WHO) region, patient population, and infection type (1995–2008). Ref. [10].

Figure 3

As illustrated by the figure, the progression of endocarditis occurs through distinct phases. Initially, the adhesion of bacterially contaminated blood to the cardiac valve endothelium, either through direct or indirect means, is facilitated by platelets. This initial stage is followed by the migration of platelets and fibrin into the affected area, leading to the formation of a vegetative mass. Concurrently, the immune system, despite the presence of substantial leukocyte concentrations, remains ineffective in impeding the progression of the infection. Consequently, this process can lead to various adverse outcomes, including cardiac valve destruction, embolisation, and uncontrollable sepsis. The blue star-shaped elements represent activated platelets (blue arrows), whereas the blue circle-shaped elements denote inactivated platelets (blue arrows). The yellow elements are representative of bacteria, and the red circle-shaped elements are blood cells.

Figure 4

As illustrated in Figure 4, shear stress-mediated binding of platelets to von Willebrand factor (VWF) is a process of paramount significance in haemostatic pathways. VWF, found in either a secreted or circulating form in the bloodstream, is utilised by endothelial cells. However, due to the A1 domain’s crucial role in platelet binding being concealed during the globular state of VWF, platelet–VWF interactions are rendered impossible. * However, in circumstances involving endothelial damage or inflammation, VWF is retained upon the endothelium, becoming exposed to the shear stress of flowing blood. This elongation process subsequently exposes the A1 domain, allowing it to interact with the GPIb receptor on platelets, thereby inducing a reduction in platelet velocity and a partial activation response. A comparable phenomenon has been observed in the context of Staphylococcus aureus binding to the A1 domain of VWF, highlighting a potential universal mechanism underpinning platelet-mediated responses to injury or inflammation. *The progressive movement of black arrows from the periphery towards the centre is suggestive of laminar flow, indicating the dynamic interaction of von Willebrand Factor (vWF) and platelets within the vascular system. The presence of a solitary black arrow signifies adherence to the endothelium in the context of peripheral laminar flow. Abbreviations in the text.

Figure 5

Staphylocytotoxins have an interference function (illustrated by the great blue arrow) with regard to the cells of both the innate (illustrated by the dark red box) and adaptive (illustrated by the green box) immune response. The cytoxins (TSS-1, staphylococcal endotoxin, and α-toxin) are cytolytic and can lyse immune cells (illustrated by the PMN, monocytes, and macrophages involved in the clearance of S. aureus [illustrated by the red arrow]). Furthermore, the ability of cytotoxins to impair the function of adaptive immune cells (green arrows), represented by both T and B lymphocytes, is well documented. Finally, it is noteworthy that cytotoxins can impair the delicate balance between innate and adaptive immune cells (blue arrows). Abbreviation: TSS-1, Toxic Shock Syndrome-1. From Nappi et al. Ref. [15].