Potential Compounds as Inhibitors of Staphylococcal Virulence Factors Involved in the Development of Thrombosis

Abstract

For many years, staphylococci have been detected mainly in infections of the skin and soft tissues, organs, bone inflammations, and generalized infections. Thromboembolic diseases have also become a serious plague of our times, which, as it turns out, are closely related to the toxic effects of staphylococci. Staphylococcus aureus, because of the presence of many different kinds of virulence factors, is capable of manipulating the host's innate and adaptive immune responses. These include toxins and cofactors that activate host zymogens and exoenzymes, as well as superantigens, which are highly inflammatory and cause leukocyte death. Coagulases and staphylokinases can control the host's coagulation system. Nucleases and proteases inactivate various immune defense and surveillance proteins, including complement components, peptides and antibacterial proteins, and surface receptors that are important for leukocyte chemotaxis. On the other hand, secreted toxins and exoenzymes are proteins that disrupt the endothelial and epithelial barrier as a result of cell lysis and disintegration of linking proteins, which ultimately increases the risk of thromboembolism. In this review, we discuss various virulence factors and substances that may inhibit their activity.

Keywords: staphylococcal infections; staphylococcal virulence factors; therapeutic strategies; thrombosis.

Figure 1

Chemical structure of resveratrol (1), naringenin (2), apigenin (3), oroxylin A (4), oroxin B (5), ponciretin (6), 1,3,6,7-tetrahydroxyxanthone (7), D-garcinon (8), kaempferol (9), and quercetin (10).

Figure 2

Chemical structure of 4-hydroxytyrosol (11), aloe-emodin (12), ω-hydroxyemodin (13), and isorhamnetin (14).

Figure 3

Chemical structure of sanguinarine (15), ethoxysanguinarine (16), 6-methoxydihydrosanguinarine (17), chelerythrine (18), dihydrochelerythrine (19), and apicidin (20).

Figure 4

Chemical structure of carvacrol (21), thymol (22), and geraniol (23).

Figure 5

Different models of the antibacterial mechanism of AMP action. The basis of these models is the interaction of AMP with negatively charged bacterial membranes, leading to increased permeability of the cell membrane, and its lysis, which ultimately leads to cell death.

Figure 6

The nanosponges consist of a polymer core covered with bilayer membranes of human RBCs, which could absorb bacterial toxins, and they transfer them away from the cellular targets. The toxins bound by the nanosponge prevent the attack on the host cell targets, protecting them from damage.

Figure 7

Chemical structure of puerarin (24) and daidzin (25).