AI-2 Prodrugs
Financiado
Development of new AI-2 prodrugs and chemical probes to study the microbiota of...
Development of new AI-2 prodrugs and chemical probes to study the microbiota of the mammalian gastro-intestinal tract
Quorum sensing allows bacteria to synchronise and regulate their behaviours. Autoinducer-2 (AI-2) is a particularly relevant signaling molecule able to promote inter-species communication. In the mammalian gut microbiota, a therap...
Quorum sensing allows bacteria to synchronise and regulate their behaviours. Autoinducer-2 (AI-2) is a particularly relevant signaling molecule able to promote inter-species communication. In the mammalian gut microbiota, a therapeutically relevant niche, interference of AI-2-mediated signaling has been shown to influence the balance of the major phyla after antibiotic treatment. Still, the mechanisms involved in this process are not known. We propose to establish novel chemical and structural based approaches to decipher the mechanisms involved in the response of the gut microbiota to AI-2 and identify mechanisms that promote beneficial responses by the symbionts while inhibiting virulence in gut pathogens. For this, we will construct chemical tools that will function as AI-2 prodrugs to orally deliver intact AI-2 to the gut. AI-2 is a highly functionalised molecule, very reactive and unstable at high concentrations, thus a prodrug strategy will protect AI-2 until its release in the gut. To gain a molecular understanding involved in response to AI-2 we will identify AI-2 sensing mechanism (receptors) in commensal and pathogenic members of the microbiota belonging to the Clostridiaceae. For that, new AI-2 fluorescent probes will be designed and synthesised. The Clostridiaceae family are relevant members in the mammalian gut. These organisms include both beneficial as well as pathogenic members and we want to identify strategies to promote the beneficial response while inhibiting the pathogenic ones to promote a healthy microbiota community. Our hypothesis is that synthetic AI-2 can help in the recovery of a healthy bacterial phyla ratio after a distress, like antibiotic treatment.
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Duración del proyecto: 23 meses
Fecha Inicio: 2022-06-03
Fecha Fin: 2024-05-31
Fecha Fin: 2024-05-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
Presupuesto
El presupuesto total del proyecto asciende a
157K€
Líder del proyecto
UNIVERSIDADE NOVA DE LISBOA
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5