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 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 Brendan Wren, London School of Hygiene and Tropical Medicine, UK
• Prof Göran Widmalm, Stockholm University, Sweden
• Prof Jeroen Codee at the University of Leiden, The Netherlands
• Prof Nina van Sorge, Amsterdam UMC, The Netherland
• Prof Nicola Stanley-Wall, School of Life Sciences, Dundee, UK

Roles

• Parental Leave Champion School of Life Sciences
• Biological Safety Officer Division of Molecular Microbiology
• ED&I Committee member

Lab members

• Dr Sowmya Ajay Castro
• Dr Saria Mansoor
• Dr Mark Reglinski
• Dr Mark McNeil
• Dr Tom Gasan
• Emma Stevenson
• Thomas Lawson

Selected publications

• Progress towards a glycoconjugate vaccine against Group A Streptococcus.  Burns K, Dorfmueller HC, Wren BW, Mawas F, Shaw HA.NPJ Vaccines. 2023 Mar 28;8(1):48. https://doi.org/10.1038/s41541-023-00639-5
   
• Agl24 is an ancient archaeal homolog of the eukaryotic N-glycan chitobiose synthesis enzymes.  Meyer BH, Adam PS, Wagstaff BA, Kolyfetis GE, Probst AJ, Albers SV, Dorfmueller HC.Elife. 2022 Apr 8;11:e67448.  https://doi.org/10.7554/eLife.67448
• Castro SA, Dorfmueller HC. 2021. A brief review on Group A Streptococcus pathogenesis and vaccine development. Royal Society Open Science. 8(3):Article 201991. https://doi.org/10.1098/rsos.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. https://doi.org/10.1042/BCJ20210158
• Wagstaff BA, Zorzoli A, Dorfmueller HC. 2021. NDP-rhamnose biosynthesis and rhamnosyltransferases: building diverse glycoconjugates in nature. Biochemical Journal. 478(4):685-701. https://doi.org/10.1042/BCJ20200505
• 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. https://doi.org/10.1038/s41589-021-00803-9
• 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. Publication
• Zorzoli A, Meyer BH, Adair E, Torgov VI, Veselovsky VV, Danilov LL, Uhrin D, Dorfmueller HC*. Group A, B, C, and G Streptococcus Lancefield antigen biosynthesis is initiated by a conserved α-D-GlcNAc-β-1,4-L-rhamnosyltransferas. J Biol Chem. 2019 Sept 10. pii: jbc.RA119.009894. doi: 10.1074/jbc.RA119.009894
• Wagstaff BA, Rejzek M, Kuhaudomlarp S, Hill L, Mascia I, Nepogodiev SA, Dorfmueller HC, Field RA*. Discovery of an RmlC/D fusion protein in the microalga Prymnesium parvum and its implications for NDP-β-L-rhamnose biosynthesis in microalgae. J Biol Chem. 2019 Apr 22. pii: jbc.RA118.006440. doi: 10.1074/jbc.RA118.006440.
• 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*. Streptococcal dTDP-L-rhamnose biosynthesis enzymes: functional characterization and lead compound identification. Mol Microbiol. 2019 Apr;111(4):951-964. doi: 10.1111/mmi.14197.
• 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*. GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD). Mol Microbiol. 2015 Dec;98(5):946-62. doi: 10.1111/mmi.13169.