Metabolic targeting of bacteria through complex carbohydrates and siderophores
Principal investigators: Andreas Faust, Silke Niemann
Former principal investigator: Ryan Gilmour
Project number: CRC 1450 A04
Project term: 01/2021–12/2028
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).
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.
2024
Margeta R, Schelhaas S, Hermann S, Schäfers M, Niemann S, Faust A. A novel radiolabelled salmochelin derivative for bacteria-specific PET imaging: synthesis, radiolabelling and evaluation. Chem Commun (Camb) 2024Abstract
2023
Ludwig N, Thörner-van Almsick J, Mersmann S, Bardel B, Niemann S, Chasan AI, Schäfers M, Margraf A, Rossaint J, Kahl BC, Zarbock A, Block H. Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung infection. Front. Immunol. 2023;14Abstract
Roll W, Faust A, Hermann S, Schäfers M. Infection Imaging: Focus on New Tracers?. J Nucl Med 2023;64: 59s-67s. Abstract
2022
Schwarz C, Buchholz R, Jawad M, Hoesker V, Terwesten-Solé C, Karst U, Linsen L, Vogl T, Hoerr V, Wildgruber M, Faber C. Fingerprints of Element Concentrations in Infective Endocarditis Obtained by Mass Spectrometric Imaging and t-Distributed Stochastic Neighbor Embedding. ACS Infect Dis 2022Abstract
2021
Axer A, Jumde RP, Adam S, Faust A, Schäfers M, Fobker M, Koehnke J, Hirsch AKH, Gilmour R. Enhancing glycan stability via site-selective fluorination: modulating substrate orientation by molecular design. Chem. Sci. 2021;12: 1286-1294. Abstract
Maisuls I, Singh J, Salto IP, Steiner ST, Kirse TM, Niemann S, Strassert CA, Faust A. Conjugated Pt(II) Complexes as Luminescence-Switch-On Reporters Addressing the Microenvironment of Bacterial Biofilms. Inorg Chem 2021;60: 11058-11069. Abstract
Masthoff M, Freppon FN, 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 2021;73: 103670. Abstract
Schwarz C, Töre Y, Hoesker V, Ameling S, Grün K, Völker U, Schulze PC, Franz M, Faber C, Schaumburg F, Niemann S, Hoerr V. Host-pathogen interactions of clinical S aureus isolates to induce infective endocarditis. Virulence 2021;12: 2073-2087. 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, Schäfers 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
Grüner 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, Löffler 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, Löffler B, Kehrel BE. Panton-Valentine Leukocidin associated with S aureus osteomyelitis activates platelets via neutrophil secretion products. Sci Rep 2018;8: 2185. Abstract
2017
Nuss AM, Beckstette M, Pimenova M, Schmühl C, Opitz W, Pisano F, Heroven AK, Dersch P. Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptomes. Proc Natl Acad Sci U S A 2017;114: E791-E800. Abstract
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, Löffler 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
