Metabolic targeting of bacteria through complex carbohydrates

Project number: CRC 1450 A04
Project term: 01/2021–12/2024

Graphical abstract
© CRC inSight

Life-threatening bacterial infections often have a non-specific clinical presentation. We aim to develop reliable diagnostic tools that enable the differentiation between sterile inflammation and bacterial infection (1). Therefore, we will design radiolabelled specific imaging probes based on oligosaccharides which are selectively taken up by prokaryotes (2). We will thereby optimize uptake and trapping efficiency in bacteria and metabolic stability in the blood.

The tracers will be evaluated in vitro in gram-positive and gram-negative bacterial strains (3) and in murine infection models in vivo, such as a vascular graft infection model (4). Other tracers and methods developed within this CRC to image activated leukocytes or to track labelled ER-HoxB8 cells will be used for correlative studies. This will prepare for a transfer of our new bacteria tracers to future clinical diagnostics (5).

Project leaders

Project member

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.

Masthoff M, Freppon F, Zondler L, Wilken E, Wachsmuth L, Niemann S, Schwarz C, Fredrich I, Havlas A, Block H, Gerwing M, Helfen A, Heindel W, Zarbock A, Wildgruber M, Faber C. Resolving immune cells with patrolling behaviour by magnetic resonance time-lapse single cell tracking. EBioMedicine: epub. Abstract

2020

Hayashi T, Axer A, Kehr G, Bergander K, Gilmour R. Halogen-directed chemical sialylation: pseudo-stereodivergent access to marine ganglioside epitopes. Chem. Sci. 2020;11: 6527-6531. Abstract

2018

Axer A, Hermann S, Kehr G, Clases D, Karst U, Fischer-Riepe L, Roth J, Fobker M, Schafers M, Gilmour R, Faust A. Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design. ChemMedChem 2018;13: 241-250. Abstract
Gruner MC, Niemann S, Faust A, Strassert CA. Axially Decorated Si(IV) -phthalocyanines Bearing Mannose- or Ammonium-conjugated Siloxanes: Comparative Bacterial Labeling and Photodynamic Inactivation. Photochem Photobiol 2018;94: 890-899. Abstract
Hoerr V, Franz M, Pletz MW, Diab M, Niemann S, Faber C, Doenst T, Schulze PC, Deinhardt-Emmer S, Loffler B. S aureus endocarditis: Clinical aspects and experimental approaches. Int J Med Microbiol 2018;308: 640-652. Abstract
Niemann S, Bertling A, Brodde MF, Fender AC, Van de Vyver H, Hussain M, Holzinger D, Reinhardt D, Peters G, Heilmann C, Loffler B, Kehrel BE. Panton-Valentine Leukocidin associated with S aureus osteomyelitis activates platelets via neutrophil secretion products. Sci Rep 2018;8: 2185. Abstract

2017

Van de Vyver H, Bovenkamp PR, Hoerr V, Schwegmann K, Tuchscherr L, Niemann S, Kursawe L, Grosse C, Moter A, Hansen U, Neugebauer U, Kuhlmann MT, Peters G, Hermann S, Loffler B. A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection: Noninvasive Imaging of Biofilm Development in Vivo. Am J Pathol 2017;187: 268-279. Abstract

2016

Galstyan A, Block D, Niemann S, Gruner MC, Abbruzzetti S, Oneto M, Daniliuc CG, Hermann S, Viappiani C, Schafers M, Loffler B, Strassert CA, Faust A. Labeling and Selective Inactivation of Gram-Positive Bacteria Employing Bimodal Photoprobes with Dual Readouts. Chemistry 2016;22: 5243-5252. Abstract
Galstyan A, Riehemann K, Schäfers M, Faust A. A combined experimental and computational study of the substituent effect on the photodynamic efficacy of amphiphilic Zn(ii)phthalocyanines. J. Mater. Chem. B 2016;4: 5683-5691. Abstract
Strobel M, Pfortner H, Tuchscherr L, Volker U, Schmidt F, Kramko N, Schnittler H-J, Fraunholz MJ, Loffler B, Peters G, Niemann S. Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S aureus strain. Clin Microbiol Infect 2016;22: 799-809. Abstract

2010

Bucher C, Gilmour R. Fluorine-directed glycosylation. Angew Chem Int Ed Engl 2010;49: 8724-8728. Abstract