Descrizione del progetto
Approfondimenti sugli elementi genetici mobili dei batteri: l’insegnamento del colera
Gli elementi genetici batterici come gli integroni sono responsabili dell’evoluzione dei batteri attraverso il trasferimento dei geni. Gli integroni mobili sono coinvolti nella comparsa della resistenza agli antibiotici, che ormai rappresenta una grande sfida sanitaria. Gli scienziati del progetto KryptonInt, finanziato dall’UE, stanno studiando il superintegrone, un integrone cromosomiale sedentario situato nel cromosoma del Vibrio cholerae, l’agente patogeno che provoca il colera. Grazie all’eliminazione del superintegrone, i ricercatori indagheranno il ruolo e il valore adattivo degli integroni in natura, e studieranno i meccanismi alla base dell’escissione dei geni in un elemento genetico mobile. I risultati del progetto riveleranno informazioni importanti sulla distribuzione dei fattori di resistenza agli antibiotici negli esseri umani, negli animali, negli alimenti e nell’ambiente.
Obiettivo
Integrons are genetic platforms that enhance bacterial evolvability through the acquisition and stockpiling of new genes encoded in mobile elements named cassettes. They are found in the chromosomes of environmental bacteria but some have acquired mobility through their association to transposons and conjugative plasmids. These mobile integrons (MI) caused the unexpected rise of multidrug resistance that is now a major threat to modern medicine, and are good proof of the adaptive power of integrons. Class 1 integrons are the most relevant MI and the major experimental model. Yet little is known about the hundreds of sedentary chromosomal integrons (SCI) that have driven bacterial evolution for eons. The paradigm of SCI is the superintegron (SI), an extremely large integron located in the chromosome of Vibrio cholerae, the causative agent of Cholera disease. Despite its role in the adaptability of one of the deadliest pathogens in history, the SI is poorly characterized because it is only functional in its native genetic background, yet its presence interferes with, and precludes all studies performed in V. cholerae. I propose to solve this paradoxical situation by deleting the SI, an ambitious project not only for its size (126 Kb) but because it is highly stabilized by 17 toxin-antitoxin systems. To do so, I have developed SeqDelTA, a novel method that is already giving excellent preliminary results. I will then use V. cholerae∆SI to study fundamental aspects of SCIs, yet out of reach. I will elucidate the functions encoded in SI cassettes to understand the role and adaptive value of integrons in nature; I will also unravel the genesis of cassettes: how a gene is exapted from its genetic context to become a mobile module; and I will explore the circulation of antibiotic resistance cassettes among humans, animals, food, and the environment with a novel biosynthetic tool (the I3C). KryptonInt will open and explore the historically inaccessible field of study of SCIs.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
- natural sciencesbiological sciencesmicrobiologybacteriology
- humanitieshistory and archaeologyhistory
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistance
- natural sciencesbiological sciencesgeneticschromosomes
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
28040 Madrid
Spagna