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Unlocking the antibiotic production potential in soil bacteria Streptomyces coelicolor

Project description

Opening the floodgate holding back novel antibiotics could wash away drug resistance

The majority of antibiotics for medical, veterinary and agricultural applications are derived from secondary metabolites produced by the Streptomyces bacteria. However, the huge number of antimicrobial compounds these bacteria currently supply is likely to be only the tip of the iceberg. Much remains unknown about their metabolic pathways. ADP-ribosylation (addition of ADP linked to the sugar ribose) is widely conserved in viruses, bacteria and eukaryotes. It is important in numerous cellular processes and has been linked to antibiotic resistance in bacteria. Following the trail of ADP-ribosylation pathways in Streptomyces, STREPUNLOCKED plans to unlock the potential of these bacteria to deliver novel and effective therapeutics that combat the perfidious and increasing emergence of multi-drug resistant microorganisms.

Objective

We live in an era where once miracle drugs – antibiotics, cease to be efficient. The rise of antibiotic resistance is an immediate major global issue. There are several layers causing the problem – misuse, overuse, lack of proper guidelines etc. The only long-term efficient solutions are – pushing more antibiotics and vaccines into the discovery pipeline. More than 70% of the naturally produced antibiotics used today come from non-pathogenic bacteria from the Streptomyces genus. These bountiful bacteria still have a lot to give, as only one-third of their secondary metabolite pathways are characterized. The rest of their potential stays locked away, i.e. inaccessible with the currently available approaches/tools. In STREPUNLOCKED project, we suggest a study of an up-and-coming pathway involved in the regulation of antibiotic production/resistance – adenosine diphosphate (ADP)-ribosylation. In order to achieve these aims, we will use a multidisciplinary approach that combines several latest mass spectrometry techniques and analyses, genetic approaches, molecular modelling and bioinformatics’ tools to characterize the novel ADP-ribosylation pathways, their signalling context, and their role in antibiotic production. Using the deep dive strategy in order to understand this pathway in Streptomyces would have multiple benefits: opening the doors to the new tool for manipulating the Streptomyces metabolism, lead the way to new lines of basic research, discovery and practical applications – such as new antibiotic compounds.

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-ST - Standard EF

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Call for proposal

(opens in new window) H2020-WF-2018-2020

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Coordinator

RUDER BOSKOVIC INSTITUTE
Net EU contribution
€ 147 463,68
Address
Bijenicka cesta 54
10000 Zagreb
Croatia
Region
Hrvatska Grad Zagreb Grad Zagreb
Activity type
Research Organisations
Links
Total cost
€ 147 463,68