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.

The Pneumococcal Protein SufC Binds to Host Plasminogen and Promotes Its Conversion into Plasmin

“…Because plasmin exhibits high proteolytic activity, it is involved in several other functions, such as tissue remodeling and inflammation, as well as thrombolysis [53]. Although plasminogen and plasmin have physiological functions in the host, bacteria can utilize them to facilitate infections [13]. For example, plasmin degrades host ECM components, such as laminin and fibronectin, and helps spread bacteria into host tissues [54].…”

“…This phenomenon has been observed mainly in groups A and B Streptococcus, and S. pneumoniae [8][9][10][11][12]. S. pneumoniae possesses proteins that function as receptors for anchoring plasminogens to bacterial cell surfaces [13]. Plasminogen recruited to the bacterial surface is converted into plasmin by the host tissue-type plasminogen activator (tPA) and/or urokinase-type plasminogen activator (uPA), allowing it to exhibit proteolytic activity [12,14].…”

Impact of Plasminogen on Clostridioides difficile Colitis

“…Some of the bacterial receptors exhibit an exceedingly high affinity for plasminogen, far surpassing that of the host's receptors-some by more than 100-fold. By leveraging plasminogen, these bacteria enhance their infectious potential, facilitating their entry and dissemination [16][17][18].…”

Pathogenicity and virulence of Yersinia

“…The breaking of these clots is thought to contribute to the pathogenesis of plague. While increased plasmin facilitates the dissemination of Y. pestis , it may also skew the inflammatory response [ 43 , 44 ].…”