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Controlling Activity of Lysogenic Phages by Small Molecule Inducers and Dysregulators

Project description

The human microbiome and its interaction with lysogenic phages

The human microbiome plays a critical role in health and disease. However, the phages infecting these microbiota have not gained sufficient attention. The majority of phages reside integrated in the genome of the microbial host as lysogenic prophages. Certain conditions induce prophages, resulting in the creation of virus particles, the destruction of the host cells and an increased production of virulence factors. The EU-funded CAPSID project aims to uncover the small molecules modulating phage induction. The objective is to isolate and characterise phage-inducing or dysregulating metabolites and identify their molecular targets. The project will apply chemical tools to study the relevant mechanisms and develop synthetic modulators of the phage-microbe systems for specific medical purposes.

Objective

The human microbiome has been increasingly in the focus of research for its importance in human health and disease. Yet, the viruses (phages) infecting these microbiota have gained much less attention. The majority of phages reside integrated in the genomes of their microbial hosts as so called lysogenic prophages.
Often, these prophages encode important toxins and other virulence related factors that, while they are beneficial to their microbial hosts, may be detrimental for the infected human. Prophages can be induced under certain conditions to resume a lytic lifestyle resulting in the production of virus particles and often in the destruction of the host cell. Frequently, however, phage induction also leads to increased production of virulence factors. In this project, we aim to uncover small molecules modulating phage induction. We will explore to what extent microbial metabolites of human microbiota act as native triggers or inhibitors of phage induction and shape the complex interspecies interactions in the microbiome. The corresponding phage inducing or dysregulating metabolites will be isolated to elucidate their chemical structure and unveil their molecular targets. We will develop chemical tools to dissect and interrogate the responsible mechanisms and finally develop customized synthetic modulators that allow us to achieve control over the activity of phage-microbe systems with specific medical relevance. The integrated approach of the CAPSID project will provide first comprehensive insights into the chemistry of microbe-phage interactions and allow to assess its role for infectious diseases and its potential for customized treatment of microbial pathogens.

Host institution

UNIVERSITAT WIEN
Net EU contribution
€ 1 992 240,00
Address
UNIVERSITATSRING 1
1010 Wien
Austria

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Region
Ostösterreich Wien Wien
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 992 240,00

Beneficiaries (1)