Use of Tetravalent Galabiose for Inhibition of Streptococcus Suis Serotype 2 Infection in a Mouse Model

Abstract

Streptococcus suis is an important swine pathogen associated with a variety of infections such as meningitis, arthritis and septicemia. The bacterium is zoonotic and has been found to cause meningitis especially in humans occupationally exposed to infected pigs. Since adhesion is a prerequisite for colonization and subsequent infection, anti-adhesion treatment seems a natural alternative to traditional treatment with antibiotics. In order to optimize the inhibitory potency a multivalency approach was taken in the inhibitor design. A synthetic tetravalent galabiose compound was chosen which had previously shown promising anti-adhesion effects with S. suis in vitro. The aim of this study was to evaluate the in vivo effects of the compound using an infection peritonitis mouse model. As such S. suis serotype 2 infection and treatment were tested in vivo and the effects were compared to the effect of treatment with penicillin.

Structural basis of the interaction between the meningitis pathogen Streptococcus suis adhesin Fhb and its human receptor

“…Specific antibodies against Fhb were also detected in patients infected with S. suis 2 [15]. Multivalent Gb2 derivatives have been constructed as drug candidates against S. suis infection [32][33][34][35]. Our report on the structure of the complex of Fhb RBD bound to Gb2 provides structural insights into the Fhbmediated bacterial and receptor interactions, and will guide the development of more effective antiadhesion drugs against S. suis infection.…”

Towards bacterial adhesion-based therapeutics and detection methods

“…Compound 32 was tested in an in vivo model. 65 The study involved a peritonitis mouse model. Although not overall signicant, notable effects were observed with the bacterial levels in the liver, lungs and spleen despite the low dose (ca.…”

Targeting TREM-1 Signaling in the Presence of Antibiotics is Effective Against Streptococcal Toxic-Shock-Like Syndrome (STSLS) Caused by Streptococcus suis

“…Until now, TREM-1 was an attractive target for the treatment of septic shock (Gibot et al, 2006 , 2007 ), sepsis (Bouchon et al, 2001 ; Gibot et al, 2004 ; Wang et al, 2012 ; Pieters et al, 2013 ; Van Bremen et al, 2013 ), inflammatory bowel disease (Holden et al, 2009 ; Genua et al, 2014 ) and chronic inflammatory disorders (Schenk et al, 2007 ), autoimmune arthritis (Murakami et al, 2009 ), corneal inflammation (Wu et al, 2011 ), and hepatocellular chronic inflammation (Wu et al, 2012 ). However, in addition to TREM-1 contributing to inflammation, TREM-1 also plays a critical role in the clearance of Pseudomonas aeruginosa (Klesney-Tait et al, 2013 ), pneumococci (Hommes et al, 2014 ), Kelbsiella pneumoniae (Lin et al, 2014 ) and the highly virulent S. suis (Yang et al, 2015 ).…”

“…It can be induced at high levels on neutrophils and monocytes and further amplifies Toll-like receptor (TLR)-initiated responses against microbial challenges, potentiating the secretion of proinflammatory cytokines with the help of the DAP12 adaptor protein in response to bacterial and fungal infections (Bouchon et al, 2001 ; Colonna and Facchetti, 2003 ; Dower et al, 2008 ). Due to the key role of TREM-1 in amplifying the inflammatory response, TREM-1 was identified as an essential regulator of innate immunity in sepsis syndrome (Nathan and Ding, 2001 ) and it was also confirmed to be an attractive target for the treatment of septic shock (Gibot et al, 2006 , 2007 ), sepsis (Bouchon et al, 2001 ; Gibot et al, 2004 ; Wang et al, 2012 ; Pieters et al, 2013 ; Van Bremen et al, 2013 ), inflammatory bowel disease (Holden et al, 2009 ; Genua et al, 2014 ), chronic inflammatory disorders (Schenk et al, 2007 ), autoimmune arthritis (Murakami et al, 2009 ), corneal inflammation (Wu et al, 2011 ), and hepatocellular chronic inflammation (Wu et al, 2012 ).…”