Community Research and Development Information Service - CORDIS

Fishing the modified protein pool for new antibiotics

Every year in the EU, around a quarter of a million people die from antibiotic-resistant bacterial infections. The key to overcoming bacterial resistance is to understand the often amazing and diverse biochemistry behind their virulence.
Fishing the modified protein pool for new antibiotics
A recently discovered way of modifying proteins after translation is the addition of adenosine monophosphate, called AMPylation. Rapidly emerging as a fundamental mechanism to regulate protein-protein interactions and cell signalling generally, bacteria use it in host-pathogen interactions. Tracking AMPylation could provide an opportunity to develop new antibiotics with a different mode of action.

The EU-funded CHEMAMP (Chemical AMPylomics: Targeting a novel host-pathogen interaction) project designed and synthesised probes to detect the occurrence of protein AMPylation. The researchers also validated a methodology for high-throughput profiling of protein AMPylation in the host and bacteria during infection.

CHEMAMP successfully identified many new AMPylated proteins and protein interaction networks in both bacterial and human cells with a bacterial infection. The team then tagged the proteins to facilitate their visualisation and isolation.

These smart AMPylated protein 'fishing pools' were thoroughly put under trial and compared with other state-of-the-art probes currently in use. Useful additional features from the other probes have been incorporated into the CHEMAMP probes to further improve their performance.

Significantly, the CHEMAMP molecules and technologies can be universally applied to other systems apart from bacterial infection. The multifunctional enrichment reagents are suitable for fluorescent visualisation and mass spectrometry-based quantification of other post-translational modifications. A prime example is protein myristoylation, a specific type of protein lipidation involved in cancer and the life cycle of Plasmodium falciparum, a malaria-causing parasite.

Major drug companies are interested in the integration of drug discovery with systems biology. The tools developed by CHEMAMP are an alternative and comprehensive way to screen and validate new drug targets.

Related information


Modified protein, antibiotic, antibiotic-resistant bacterial infection, AMPylation, probes
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