Structure elucidation and study of the biosynthesis of glycosylglycerolipids and teichoic acids of Streptococcus suis and their impact on pathogenicity

• Applicant: Dr. Nicolas Gisch
• Subject Area: Veterinary Medical Science ; Analytical Chemistry ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536971318

Teichoic acids (TAs) are essential components of the cell wall of the zoonotic pathogen Streptococcus suis that mainly infects pigs. The structure of its lipoteichoic acid (LTA) was described by us and we could show that S. suis is the first described bacterium, which produces an LTA with two sequential linked structural types. On the one hand we showed the presence of a type I LTA, which is characterized by its poly-glycerolphosphate chain. On the other hand, we were able to show that to this first LTA to some extent further complex, glycosylated building blocks are repetitively added. We already proved the presence of two different classes of these complex LTA molecules within S. suis serotype 2 strains. First experiments using cell-based assays and murine infection models with a genetically modified strain that was no longer capable of glycosylating its LTA indicated the high importance for pathogenicity of this strain. One aim of this project is the screening for other structural LTA variants within other serotypes that frequently occur especially in Germany and North America. Moreover, we will analyze the sequence type (ST) 1 and 25 strains of serotype 2, in which the complex glycosylated LTA have been initially found, with regard to their LTA biosynthesis by deletion of selective genes, especially those putatively involved in the glycosylation process. By this, we aim to gain detailed functional insights. Not much is known about the wall teichoic acid (WTA) and its importance for pathogenicity of S. suis to date. The proof of the presence of a WTA in the S. suis cell wall on the molecular level has not been done yet. In preliminary work, we have been able to show the presence of two distinct cell-wall attached polysaccharides in S. suis. One is the already known capsular polysaccharide, the other polymer displays structural features clearly pointing towards the existence of a WTA. The general chemical structure of this WTA as well as putative ST-specific variants in serotype 2 strains and in other serotypes will be one focus point of this project. The aim is to unravel if the WTA has a completely conserved structure among all strains or if ST-/serotype-specific variants as described for the LTA can be observed. The cell wall of S. suis contains three different glycoglycerolipids, but only one of these represents the glycolipid anchor of the LTA. Glycoglycerolipids of other bacteria have already been described to interact with the C-type receptor Mincle. In this part of project, we will systematically analyze the interaction of Mincle with S. suis glycoglycerolipids and similar molecules of known structure isolated from other bacteria. In summary, the whole project shall provide detailed insights into the structure and biosynthesis pathways of glycoglycerolipids and TAs in S. suis, to be finally able to propose new potential drug targets against this zoonotic pathogen.

• DFG Programme: Research Grants
• International Connection: Canada
• Cooperation Partners: Professor Dr. Nahuel Fittipaldi; Professor Dr. Marcelo Gottschalk