Tight Junction Physiology in Enteropathogenic Infections

Tight junctions are dynamic assemblies of transmembrane and cytoplasmic proteins that seal the paracellular space between intestinal epithelial cells, regulating ion flux and preventing microbial invasion. In enteropathogenic infections, pathogens such as enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli and Brachyspira species deliver effector proteins into host cells via a type III secretion system, targeting key junctional components. These effectors—among them EspF, Map and novel adhesins—interfere with tight junction assembly, transcriptional expression and protein turnover, leading to increased intestinal permeability, diarrhoeal disease and systemic inflammation. Understanding the molecular interplay between bacterial virulence factors and host junctional machinery has global health implications, offering routes to restore barrier integrity and reduce morbidity in vulnerable populations.

Research from Nature Portfolio

Recent studies have dissected the distinct contributions of EspF and Map in tight junction disruption. In vitro models constitutively expressing each effector revealed that EspF down-regulates transcripts of claudin-1, occludin and ZO-1, whereas Map selectively reduces claudin-1 mRNA. Both effectors promote lysosomal degradation of existing junctional proteins and inhibit recruitment of new components during junction assembly. Mapping of host–effector interactions identified Map binding to non-muscle myosin II and EspF interaction with ZO-1, emphasising diverging mechanisms by which these effectors undermine tight junction integrity.

Tight Junction Physiology in Enteropathogenic Infections publication trend

The graph below shows the total number of articles in tight junction physiology in enteropathogenic infections across all publications each year (not limited to Nature Index journals).

Technical terms

Tight junction: A multi-protein complex at the apical region of epithelial cells that controls paracellular permeability and maintains barrier integrity.

Type III secretion system: A needle-like bacterial apparatus for the direct injection of effector proteins into host cells.

Effector protein: A virulence factor delivered by pathogens to manipulate host cell structure or signalling.

Claudins: A family of transmembrane proteins forming the backbone of tight junction strands and regulating ion selectivity.

ZO-1: A cytoplasmic scaffold protein linking transmembrane tight junction proteins to the actin cytoskeleton.

References

1. BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection. Gut Microbes (2024).
2. The C-terminal proline-rich repeats of Enteropathogenic E. coli effector EspF are sufficient for the depletion of tight junction membrane proteins and interactions with early and recycling endosomes. Gut Pathogens (2024).
3. Enteropathogenic E. coli effectors EspF and Map independently disrupt tight junctions through distinct mechanisms involving transcriptional and post-transcriptional regulation. Scientific Reports (2018).