University of Dundee

Dr Helge Dorfmueller

Investigation of streptococcal cell wall biogenesis and glycoconjugate vaccine development
Royal Society and Wellcome Trust Sir Henry Dale Fellow
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 386203, int ext 86203


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 from the HD laboratory is on the biosynthesis pathway of the Group A Carbohydrate. In order to reveal details into the biosynthesis of this Streptococcus pyogenes virulence factor, we are applying a range of disciplines ranging from molecular biology, synthetic biology, biochemistry, mass-spectrometry and structural biology.

This research is conducted in collaboration with:

Prof Mike Ferguson, University of Dundee, UK

Dr Nina van Sorge at the University Medical Center Utrecht, The Netherlands  

Dr Jeroen Codee at the University of Leiden, The Netherlands



Selected Publications:

Arends DW, Miellet WR, Langereis JD, Ederveen THA, van der Gaast-de Jongh CE, van Scherpenzeel M, Knol MJ, van Sorge NM, Lefeber DJ, Trzciński K, Sanders EAM, Dorfmueller HC, Bootsma HJ, de Jonge MI. 2021. Examining the distribution and impact of single nucleotide polymorphisms in the capsular locus of Streptococcus pneumoniae serotype 19A. Infection and Immunity. 89(11):Article e00246-21.

Castro SA, Dorfmueller HC. 2021. A brief review on Group A Streptococcus pathogenesis and vaccine development. Royal Society Open Science. 8(3):Article 201991.

King H, Ajay Castro S, Pohane AA, Scholte CM, Fischetti VA, Korotkova N, Nelson DC, Dorfmueller HC. 2021. Molecular basis for recognition of the Group A Carbohydrate backbone by the PlyC streptococcal bacteriophage endolysin. Biochemical Journal. 478(12):2385-2397.

Wagstaff BA, Zorzoli A, Dorfmueller HC. 2021. NDP-rhamnose biosynthesis and rhamnosyltransferases: building diverse glycoconjugates in nature. Biochemical Journal. 478(4):685-701.

Zamakhaeva S, Chaton CT, Rush JS, Ajay Castro S, Kenner CW, Yarawsky AE, Herr AB, van Sorge NM, Dorfmueller HC, Frolenkov GI, Korotkov KV, Korotkova N. 2021. Modification of cell wall polysaccharide guides cell division in Streptococcus mutans. Nature Chemical Biology. 17:878-887.

Lenardon MD, Sood P, Dorfmueller H, Brown AJP, Gow NAR. 2020. Scalar nanostructure of the Candida albicans cell wall; a molecular, cellular and ultrastructural analysis and interpretation. Cell Surface.

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.

*corresponding author

All publications can be found here: