Dr Helge Dorfmueller
The cell wall of Gram-positive bacteria consists of an intricate network of proteins, peptidoglycan, and secondary cell wall structures (SCWS) that are covalently linked to the peptidoglycan. Teichoic or teichuronic acids are typical and well-studied SCWS in Gram-positive bacteria and play an important role in normal cell function and infection. Interestingly, many β-hemolytic streptococcal species appear to lack expression of typical teichoic or teichuronic acid structures and instead express a rhamnose-rich polysaccharide, which comprises approximately half of the cell wall by weight. Historically, expression of these evolutionary conserved glycans underlies classification of β-hemolytic streptococci in Lancefield groups (A, B, C, G...), a feature that is still made use of and applied in contemporary rapid test kits to diagnose and classify streptococcal infections.
The current research focus is on the biosynthesis pathway of the essential sugar nucleotide dTDP-rhamnose. Combinations of methods are applied to conduct functional and structural studies on the enzymes of the dTDP-rhamnose biosynthesis pathway.
This research is conducted in collaboration with:
Group A, B, C, and G Streptococcus Lancefield antigen biosynthesis is initiated by a conserved α-D-GlcNAc-β-1,4-L-rhamnosyltransferas. Zorzoli A, Meyer BH, Adair E, Torgov VI, Veselovsky VV, Danilov LL, Uhrin D, Dorfmueller HC*. J Biol Chem. 2019 Sept 10. pii: jbc.RA119.009894. doi: 10.1074/jbc.RA119.009894
Discovery of an RmlC/D fusion protein in the microalga Prymnesium parvum and its implications for NDP-β-L-rhamnose biosynthesis in microalgae. Wagstaff BA, Rejzek M, Kuhaudomlarp S, Hill L, Mascia I, Nepogodiev SA, Dorfmueller HC, Field RA*. J Biol Chem. 2019 Apr 22. pii: jbc.RA118.006440. doi: 10.1074/jbc.RA118.006440.
Streptococcal dTDP-L-rhamnose biosynthesis enzymes: functional characterization and lead compound identification. van der Beek SL, Zorzoli A, Çanak E, Chapman RN, Lucas K, Meyer BH, Evangelopoulos D, de Carvalho LPS, Boons GJ, Dorfmueller HC*, van Sorge NM*. Mol Microbiol. 2019 Apr;111(4):951-964. doi: 10.1111/mmi.14197.
GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD). van der Beek SL, Le Breton Y, Ferenbach AT, Chapman RN, van Aalten DM, Navratilova I, Boons GJ, McIver KS, van Sorge NM*, Dorfmueller HC*.Mol Microbiol. 2015 Dec;98(5):946-62. doi: 10.1111/mmi.13169.
A structural and biochemical model of processive chitin synthesis. Dorfmueller HC*, Ferenbach AT, Borodkin VS, van Aalten DM*. J Biol Chem. 2014 Aug 15;289(33):23020-8. doi: 10.1074/jbc.M114.563353.
All publications can be found here: