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Design of a live-attenuated bacterial vaccine using effector network engineering

ABSTRACT: Enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium (CR) are extracellular enteric attaching and effacing (A/E) pathogens of humans and mice, respectively. Their virulence relies on intimate bacterial attachment and a network of type III secretion system effectors. Here, through systematic reduction and redesign of the effector network in CR, we develop an attenuated strain, CRV (CR Vaccine), encoding a subset of ten effectors. CRV colonises C57BL/6 mice ~100-fold lower than wild type CR (CRWT) without causing overt pathogenesis. Moreover, C3H/HeN mice, which succumb to CRWT infection, survive CRV challenge. Vaccination with CRV confers protection against subsequent CRWT infection in both mouse strains. Serological analysis reveals a repertoire of dominant CR antigens and shows that CRWT and CRV immunisation elicits comparable B cell and antibody responses, which is contingent on intimate bacterial attachment. A corresponding EPEC strain (E. coli Vaccine, ECV) effectively colonises epithelial cells in a gut-on-chip model. These findings establish effector network minimisation as a generalisable strategy for rational attenuation and live-attenuated vaccine design against A/E pathogens.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli Ko11fl Citrobacter Rodentium Icc168

SUBMITTER: Graeme Benstead-Hume

LAB HEAD: Jytoi Choudhary

PROVIDER: PXD080490 | Pride | 2026-07-06

REPOSITORIES: Pride

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			Action	DRS
	20240513_SJ_Frankel_Band_01.msf	Msf
	20240513_SJ_Frankel_Band_01.pdResult	Other
	20240513_SJ_Frankel_Band_01.raw	Raw
	20240513_SJ_Frankel_Band_02.msf	Msf
	20240513_SJ_Frankel_Band_02.pdResult	Other

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