Streptococcus suis Serotype 2 Interactions with Human Brain Microvascular Endothelial Cells

Abstract

Streptococcus suis serotype 2 is a worldwide causative agent of many forms of swine infection and is also recognized as a zoonotic agent causing human disease, including meningitis. The pathogenesis of S. suis infections is poorly understood. Bacteria circulate in the bloodstream in the nonimmune host until they come in contact with brain microvascular endothelial cells (BMEC) forming the blood-brain barrier. The bacterial polysaccharide capsule confers antiphagocytic properties. It is known that group B streptococci (GBS) invade and damage BMEC, which may be a primary step in the pathogenesis of neonatal meningitis. Interactions between S. suis and human endothelial cells were studied to determine if they differ from those between GBS and endothelial cells. Invasion assays performed with BMEC and human umbilical vein endothelial cells demonstrated that unlike GBS, S. suis serotype 2 could not invade either type of cell. Adherence assays showed that S. suis adhered only to BMEC, whereas GBS adhered to both types of cell. These interactions were not affected by the presence of a capsule, since acapsular mutants from both bacterial species adhered similarly compared to the wild-type strains. Lactate dehydrogenase release measurements indicated that some S. suis strains were highly cytotoxic for BMEC, even more than GBS, whereas others were not toxic at all. Cell damage was related to suilysin (S. suis hemolysin) production, since only suilysin-producing strains were cytotoxic and cytotoxicity could be inhibited by cholesterol and antisuilysin antibodies. It is possible that hemolysin-positive S. suis strains use adherence and suilysin-induced BMEC injury, as opposed to direct cellular invasion, to proceed from the circulation to the central nervous system.

Streptococcus iniaeVirulence Is Associated with a Distinct Genetic Profile

“…Representative disease-associated and commensal strains of S. iniae (9117 and 9085, respectively) adhered equally to the surface of HEp-2 cells (ϳ10 5 clearly enclosed within membrane-bound vesicles (Fig. 4).…”

“…Another distinct feature of many streptococcal species, such as GAS, GBS, S. pneumoniae and S. suis (5,21,30,31), is the ability to adhere to host tissue and invade intracellularly where invasion is defined as bacterial internalization within nonphagocytic cells in an in vitro system. Adherence and invasion may bestow resistance to host clearance mechanisms or facilitate systemic dissemination by breaching cell barriers.…”

Isolation and characterization of α-enolase, a novel fibronectin-binding protein from Streptococcus suis

“…Once in the bloodstream, S. suis resists phagocytosis and killing by neutrophils and monocytes (Chabot-Roy et al, 2006;Charland et al, 1998;Segura et al, 1998;Smith et al, 1999). In the event that S. suis fails to cause acute fatal septicaemia, bacteria are able to reach the CNS via different mechanisms that are only partially elucidated, such as adhesion to, with or without toxicity, and invasion of brain microvascular endothelial cells (BMEC) (Benga et al, 2005;Charland et al, 2000;Vanier et al, 2004) and/or choroid plexus epithelial cells (Tenenbaum et al, 2005(Tenenbaum et al, , 2006. In fact, interactions of S. suis with both fibronectin and plasminogen may play a role in some of these mechanisms.…”

“…The capsule polysaccharide (CPS) is a critical virulence factor, given that unencapsulated isogenic mutants are completely avirulent and rapidly cleared from the circulation in pig and mouse infection models (Charland et al, 2000;Smith et al, 1999). However, non-virulent strains are also encapsulated, indicating that the virulence of this pathogen is a multifactorial process .…”

Production of Muraminidase-Released Protein (MRP), Extracellular Factor (EF) and Suilysin by field isolates of Streptococcus suis capsular types 2, 1/2, 9, 7 and 3 isolated from swine in France

“…Separated proteins were further transferred to nitrocellulose membrane and after blocking unreacted sites with milk (2%), blots were incubated with a monoclonal antibody against MRP (kindly provided by H.J. Wisselink, ID-DLO, Lelystad, The Netherlands) or with monospecific polyclonal antibodies against EF and Suilysin, respectively, which were produced as previously described [5,13]. Peroxydase-labeled antimouse or anti-rabbit immunoglobulins were added and revelation of bound antibodies was visualised after the addition of 4-chloro-1-naphtol (Sigma-Aldrich, St Quentin Fallavier, France).…”