Abstract
BackgroundStreptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall.MethodsHuman omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48 h, contractile response to noradrenaline was measured, and levels of nitrite/nitrate and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in the incubation medium were measured. A second set of arteries were incubated with or without main components of plasma (immunoglobulin G, albumin or fibrinogen), in the presence of M1 protein followed by cytokine measurement.ResultsArtery segments incubated with M1 protein and plasma contracted weaker in response to noradrenaline, and levels of IL-6 and IL-8 were significantly higher compared to after incubation with M1 protein alone. Incubation with M1 protein and fibrinogen resulted in elevated levels of IL-6 and IL-8, while incubation with M1 protein and albumin or immunoglobulin G did not affect the levels. Neither any of the other cytokines nor nitrite/nitrate was detected in the medium in any of the incubation conditions.ConclusionsThe study shows that M1 protein of Streptococcus pyogenes has a direct effect on the human vascular wall in the presence of plasma, demonstrated both as a diminished contractile response to noradrenaline and increased cytokine production. The effect of plasma was attributed to fibrinogen. The findings suggest that M1 protein contributes to the development of septic shock through impairment of the contractility of the vascular wall.
Highlights
Streptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis
The Gram-positive bacterium Streptococcus pyogenes is one of the pathogens causing severe sepsis. It possesses a group of virulence factors, M proteins [3], some of which stimulate immune cells leading to a cytokine storm and sepsis, resulting in tissue damage, disseminated intravascular coagulation and organ dysfunction [4]
In the present study we have shown that human arteries, incubated with the streptococcal virulence factor M1 protein in vitro, have a reduced contractile smooth muscle response to noradrenaline, the most frequently used vasoconstrictor in critically ill patients
Summary
Streptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. The Gram-positive bacterium Streptococcus pyogenes is one of the pathogens causing severe sepsis. It possesses a group of virulence factors, M proteins [3], some of which stimulate immune cells leading to a cytokine storm and sepsis, resulting in tissue damage, disseminated intravascular coagulation and organ dysfunction [4]. M proteins are present on the surface of Group A, C and G streptococci, but can be found solubilized in plasma. They comprise of over 200 serotypes determined by gene type, and M protein serotyping is used as an epidemiological marker to identify streptococcal isolates
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