Target intelligence / Profile preview

Intimin-Translocated intimin receptor complex (Intimin-Tir)

Target
Intimin-Tir
Molecular classification
Bacterial adhesin, Bacterial effector protein, Protein-protein interaction, Receptor-ligand complex
01

Overview

The Intimin-Tir complex is a pivotal protein-protein interaction between the bacterial outer membrane protein Intimin and the Translocated intimin receptor (Tir) [1, 3]. This interaction is the defining feature of infections caused by attaching and effacing (A/E) pathogens, most notably Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) [1, 11]. During the infection process, the bacterium utilizes a Type III Secretion System (T3SS) to translocate Tir into the host cell plasma membrane [2, 14]. Once integrated, Tir serves as a high-affinity receptor for Intimin, which is displayed on the bacterial surface [3, 11]. This binding event triggers a complex signaling cascade within the host cell, leading to the reorganization of the actin cytoskeleton and the formation of characteristic pedestal-like structures beneath the adherent bacteria [1, 8, 11]. Because the Intimin-Tir interaction is essential for stable colonization and subsequent pathogenesis, it represents a significant target for anti-virulence therapeutic strategies [7, 20]. Current research focuses on developing small molecule inhibitors, monoclonal antibodies, and peptides that can disrupt this interaction to prevent bacterial attachment and disease progression without the selective pressure of traditional antibiotics [19, 20, 21].

Other names
eae-Tir interactionIntimin-Tir interactioneaeA-espE interactionIntimin-Tir complex
02

Mechanism of action

Inhibition of bacterial attachment to host cells and prevention of attaching and effacing (A/E) lesion formation [7, 20].

03

Biological functions

Bacterial adhesionPedestal formationHost cell cytoskeleton rearrangementActin polymerizationAttaching and effacing (A/E) lesion formation
04

Disease associations

InfectionDiarrheaHemorrhagic colitisHemolytic uremic syndrome
05

Safety considerations

Specificity for pathogenic strains [20]Risk of Shiga toxin release in EHEC infections [1, 4]
06

Interacting drugs

Aurodox (experimental)

2 more in the full profile.

07

Biomarkers

eae gene [4]tir gene [4]Attaching and effacing (A/E) lesions [1, 11]

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