Activation of the contact-phase system on bacterial surfaces - A clue to serious comlications in infections deseases

Fever, hypotension and bleeding disorders are common symptoms of sepsis and septic shock. The activation of the contact-phase system is thought to contribute to the development of these severe disease states by triggering proinflammatory and procoagulatory cascades; however, the underlying molecular mechanisms are obscure. Here we report that the components of the contact-phase system are assembled on the surface of Escherichia coil and Salmonella through their specific interactions with fibrous bacterial surface proteins, curli and fimbriae. As a consequence, the proinflammatory pathway is activated through the release of bradykinin, a potent inducer of fever, pain and hypotension. Absorption of contact-phase proteins and fibrinogen by bacterial surface proteins depletes relevant coagulation factors and causes a hypocoagulatory state. Thus, the complex interplay of microbe surface proteins and host contact-phase factors may contribute to the symptoms of sepsis and septic shock

Modulation of the Coagulation System During Severe Streptococcal Disease.

Haemostasis is maintained by a tightly regulated coagulation system that comprises platelets, procoagulant proteins, and anticoagulant proteins. During the local and systemic response to bacterial infection, the coagulation system becomes activated, and contributes to the pathophysiological response to infection. The significant human pathogen, Streptococcus pyogenes has multiple strategies to modulate coagulation. This can range from systemic activation of the intrinsic and extrinsic pathway of coagulation to local stimulation of fibrinolysis. Such diverse effects on this host system imply a finely tuned host-bacteria interaction. The molecular mechanisms that underlie this modulation of the coagulation system are discussed in this review

Disease manifestations and pathogenic mechanisms of group A Streptococcus

Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority