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Natural products and their cellular targets: A multidisciplinary strategy for antibacterial drug discovery

Objective

After decades of successful treatment of bacterial infections with antibiotics, formerly treatable bacteria have developed drug resistance and consequently pose a major threat to public health. To address the urgent need for effective antibacterial drugs we will develop a streamlined chemical-biology platform that facilitates the consolidated identification and structural elucidation of natural products together with their dedicated cellular targets. This innovative concept overcomes several limitations of classical drug discovery processes by a chemical strategy that focuses on a directed isolation, enrichment and identification procedure for certain privileged natural product subclasses. This proposal consists of four specific aims: 1) synthesizing enzyme active site mimetics that capture protein reactive natural products out of complex natural sources, 2) designing natural product based probes to identify their cellular targets by a method called activity based protein profiling , 3) developing a traceless photocrosslinking strategy for the target identification of selected non-reactive natural products, and 4) application of all probes to identify novel enzyme activities linked to viability, resistance and pathogenesis. Moreover, the compounds will be used to monitor the infection process during invasion into eukaryotic cells and will reveal host specific targets that promote and support bacterial pathogenesis. Inhibition of these targets is a novel and so far neglected approach in the treatment of infectious diseases. We anticipate that these studies will provide a powerful pharmacological platform for the development of potent natural product derived antibacterial agents directed toward novel therapeutic targets.

Field of science

  • /medical and health sciences/health sciences/public and environmental health
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance
  • /medical and health sciences/health sciences/infectious disease
  • /natural sciences/biological sciences/microbiology/bacteriology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

ERC-2010-StG_20091028
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

TECHNISCHE UNIVERSITAET MUENCHEN
Address
Arcisstrasse 21
80333 Muenchen
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 500 000
Principal investigator
Stephan Axel Sieber (Prof.)
Administrative Contact
Ulrike Ronchetti (Mrs.)

Beneficiaries (1)

TECHNISCHE UNIVERSITAET MUENCHEN
Germany
EU contribution
€ 1 500 000
Address
Arcisstrasse 21
80333 Muenchen
Activity type
Higher or Secondary Education Establishments
Principal investigator
Stephan Axel Sieber (Prof.)
Administrative Contact
Ulrike Ronchetti (Mrs.)