The Recruitment and Activation of Plasminogen by Bacteria-The Involvement in Chronic Infection Development

Abstract

The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen-the precursor of the important plasma serine proteinase, plasmin-are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases.

Keywords: bacterial infection; enolase; fibrinolysis; periodontal disease; plasmin; plasminogen.

Figure 1

Network visualization of terms related to the relationship between plasminogen and bacterial infections noted in the scientific literature in the years 1992–2023 based on the Web of Science database (VOSviewer version 1.6.19).

Figure 2

Mechanisms of the activation of the plasma fibrinolytic system by the host and by bacterial factors. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license. HPG—plasminogen, PL—plasmin, uPA—urokinase, tPA—tissue plasminogen activator, BP—bacterial proteinase, PA—plasminogen activator, PR—plasminogen receptor, and FDP—fibrin degradation products.

Figure 3

Proposed sites of interaction of bacterial enolases with individual plasminogen domains. PAN—plasminogen–apple–nematode domain, K1–K5—kringle domains, and S1—catalytic domain with serine protease activity.

Figure 4

Advantages and disadvantages of fibrin clot formation and fibrinolysis system activation for human host and bacteria during host–pathogen interactions.