ECOSTRAT
Financiado
Interrogating the diversity of gut colonization strategies in multidrug resistan...
Interrogating the diversity of gut colonization strategies in multidrug resistant E. coli to deduce robust competitive exclusion based treatments
The rise of multidrug-resistant bacteria limits the options to treat critically ill patients. In 2015, Escherichia coli producing Extended Spectrum β-Lactamases (ESBL) were the leading cause of death attributable to antibiotic re...
The rise of multidrug-resistant bacteria limits the options to treat critically ill patients. In 2015, Escherichia coli producing Extended Spectrum β-Lactamases (ESBL) were the leading cause of death attributable to antibiotic resistant bacteria in Europe. The failure to address these infections using standard antibiotherapy calls for better understanding of how these bacteria evolve in order to develop new treatments.
Presence of resistance and virulence genes correlates with high prevalence in ESBL clones. Since the intestinal tract of mammals represents a major ecological niche for E. coli, gut colonization ability must have predisposed certain clones to evolutionary success during the antibiotic era. In particular, competition against the gut microbiota should select for colonization factors that predate the acquisition of resistance.
To test this hypothesis, we will compare strategies for gut colonization in ESBL clones of different prevalence in absence of antibiotics. Using mice, we will be able to modulate selective pressures exerted by the intestinal microbiota. We will compare gut colonization factors in ESBL clones by performing parallel high-throughput genetic screening in conventional mice (aim 1). We will analyze adaptability and the stability of resistance and virulence genes during long-term colonization (aim 2). Subsequent competitions in gnotobiotic mice harboring permissive microbiota will allow us to deduce functions needed for colonization in the presence of a competitive microbiota. In aim 3, we will measure the impact of competitors transmitted from cohabitant to infected mice on the duration of ESBL E. coli carriage and assess potential synergies with the adaptive immunity in vaccinated hosts.
Overall, we will unravel with unprecedented depth the general principles of intestinal colonization in ESBL E. coli, shed new light on the global success of prevalent clones and conceptualize robust antibiotic-free competition-based treatments.
ver más
Duración del proyecto: 67 meses
Fecha Inicio: 2021-05-25
Fecha Fin: 2026-12-31
Fecha Fin: 2026-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-05-25
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-COG:
ERC CONSOLIDATOR GRANTS
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITAT BASEL
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
251.51K€ |
Participante