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@article{Frankel:2026:10.1038/s41467-026-76138-7,
author = {Frankel, G},
doi = {10.1038/s41467-026-76138-7},
journal = {Nature Communications},
title = {Design of a live-attenuated bacterial vaccine using effector network engineering},
url = {http://dx.doi.org/10.1038/s41467-026-76138-7},
year = {2026}
}
TY - JOUR
AB - 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, including the O-antigen, the virulence factors intimin, EspA and Tir and the outer membrane proteins Lpp, OmpA, MetQ and CARC (an AIDA-like autotransporter). We show 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 bacterial attenuation and live-attenuated vaccine design.
AU - Frankel,G
DO - 10.1038/s41467-026-76138-7
PY - 2026///
SN - 2041-1723
TI - Design of a live-attenuated bacterial vaccine using effector network engineering
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-026-76138-7
UR - https://www.nature.com/articles/s41467-026-76138-7
ER -