The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis

Abstract

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide range of pathologies ranging from mild pharyngitis and impetigo to severe invasive soft tissue infections. Despite the continuing susceptibility of the bacterium to β-lactam antibiotics there has been an unexplained resurgence in the prevalence of invasive GAS infection over the past 30 years. Of particular importance was the emergence of a GAS-associated sepsis syndrome that is analogous to the systemic toxicosis associated with TSST-1 producing strains of Staphylococcus aureus. Despite being recognized for over 20 years, the etiology of GAS associated sepsis and the streptococcal toxic shock syndrome remains poorly understood. Here we review the virulence factors that contribute to the etiology of GAS associated sepsis with a particular focus on coagulation system interactions and the role of the superantigens in the development of streptococcal toxic shock syndrome.

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

“…Superantigens bind to the beta-chain of CD4 ϩ T cells and MHC class II molecules on B cells, monocytes, and dendritic cells, resulting in the overstimulation of the inflammatory response and subsequent systemic toxicity, tissue necrosis, organ failure, and shock (357). Each superantigen is specific for a distinct repertoire of V␤ gene products and can therefore activate up to 20% of circulating naive T cells (358). Rampant T-cell activation has also been shown to occur following the uptake of superantigens by dendritic cells in vivo, further contributing to the proinflammatory cascade (359).…”

Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer

“…S. pyogenes infections significantly impact host coagulation as shown by decreased fibrinogen levels in the plasma, increased levels of fibrin degradation products, and up to a 50% reduction in platelet count [71, 72]. Killed bacteria, washed to remove any non- S. pyogenes proteins, increase the production of TF from cells, as shown in vitro [71].…”

“…Killed bacteria, washed to remove any non- S. pyogenes proteins, increase the production of TF from cells, as shown in vitro [71]. The M protein complexes with up to four fibrinogen molecules and platelets already activated by anti- S. pyogenes Ab [72, 73]. These activated platelets then interact with neutrophils and monocytes to increase the release of TF, increasing clotting and releasing heparin-binding protein.…”

Fisiopatología de la sepsis por gram positivos

“…En Estados Unidos se han encontrado cerca de 200 000 casos de sepsis por gram positivos frente a aproximadamente 150 000 casos de sepsis de gram negativos, siendo sus principales representantes Staphylococcus aureus y Streptococcus pyogenes, quienes tanto en países en desarrollo como en países industrializados, acompañadas de las Enterobacteriaceas sp, son la principal causa de sepsis tardía en neonatos. Adicionalmente, en los últimos 20 años, se ha hecho protagonista de sepsis el Streptococcus pyogenes del grupo A invasivo (GAS), considerado un importante problema de epidemiología mundial y responsable en un 10 -16% de la sepsis en infecciones en las que es su principal agente etiológico como infecciones puerperales, artritis séptica, fascitis necrotizante, celulitis, entre otras; y 20% de la sepsis en las admisiones en unidades de cuidados intensivos en casos de infección invasiva por este microorganismo (1)(2)(3)(4).…”