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Photo Control of Persisters Targeting the Magic Spot

The abusive use of antibiotics has led to multidrug-resistant bacteria and the acute threat of a post-antibiotic era. However, apart from resisters, there is a subgroup of bacteria called persisters that surviveby recalcitrance to... ver más

31/08/2025

ALU-FR

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

ALBERTLUDWIGSUNIVERSITAET FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-01-22

ERC-2019-COG: ERC Consolidator Grant

I+D

Cerrada hace 5 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

ALU-FR

2.00M€ | Lider

INTEGRAL BIOENERGIES SYSTEMS...

400.00K€ | Participante

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Duración del proyecto: 67 meses Fecha Inicio: 2020-01-22
Fecha Fin: 2025-08-31

Líder del proyecto

ALBERTLUDWIGSUNIVERSITAET FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The abusive use of antibiotics has led to multidrug-resistant bacteria and the acute threat of a post-antibiotic era. However, apart from resisters, there is a subgroup of bacteria called persisters that surviveby recalcitrance to antibiotic treatment. Persisters are not resistant to antibiotics but simply survive by metabolic shutdown. Upon withdrawal of antibiotics, these persisters resuscitate and regenerate the colony. They are heavily involved in failure of antibiotic treatment and the development of chronic infections. Bacterial persistence is controlled by the stringent response, which itself is mediated by hyperphosphorylated nucleotides, known as the magic spot (MS) nucleotides or (p)ppGpp. The importance of the stringent response, its omnipresence in the domain of bacteria, its connection to persister formation and tolerance to (antibiotic) stress, and its absence in mammals has led to significant research in microbiology. However, until recently these activities have not been paralleled by the development of chemical biology approaches. The current proposal aims to fill this gap by research into (1) synthetic methodology targeting the magic spot nucleotides and their analogs, (2) tools to identify target proteins of (p)ppGpp, and more generally (p)ppNpp (3) analytical approaches to extract, resolve, and quantify (p)ppGpp, (4) strategies to control the stringent response and persister formation with light (5) inhibitors of the stringent response. These new tools will enable a detailed understanding of the stringent response and thus ultimately help in the design of new antibiotics effective against persisters. The goal is to develop methods to force bacteria into the persistent state or inversely wake them up by using light and small molecules. Forcing bacteria out of persistence and blocking their entry into this state in combination with antibiotic treatment is a highly promising strategy to avoid the development of chronic bacterial infections.

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