Target intelligence / Profile preview

Type III secretion system apparatus proteins (T3SS)

Target
T3SS
Molecular classification
Protein secretion system, Virulence factor, Transporter, Multi-protein complex
01

Overview

The Type III secretion system (T3SS) apparatus, often referred to as the "injectisome," is a sophisticated multi-protein complex found in many pathogenic Gram-negative bacteria, including Salmonella, Shigella, and Pseudomonas aeruginosa (1). Its primary biological function is to serve as a molecular syringe that translocates bacterial effector proteins directly from the bacterial cytoplasm into the cytosol of eukaryotic host cells (2). These effectors manipulate host signaling pathways to facilitate bacterial entry, suppress immune responses, and promote intracellular survival (3). Because the T3SS is essential for pathogenesis but not for bacterial growth outside a host, it is considered a prime target for anti-virulence therapeutic strategies (4). Small molecule inhibitors, such as salicylidene acylhydrazides and thiazolidinones, are being developed to block the assembly or function of the T3SS, thereby disarming the pathogen without exerting the high selective pressure for resistance associated with traditional antibiotics (5). (1) Galán, J. E., et al. (2014) EcoSal Plus; (2) Cornelis, G. R. (2006) Nature Reviews Microbiology; (3) Coburn, B., et al. (2007) Clinical Microbiology Reviews; (4) Keyser, P., et al. (2008) Future Microbiology; (5) Duncan, M. C., et al. (2012) Methods in Enzymology.

Other names
InjectisomeContact-dependent secretion systemHrp systemT3S apparatusType III injectisome
02

Mechanism of action

Inhibition of the assembly or function of the needle complex, blockade of the T3SS ATPase (e.g., EscN/VscN), or prevention of effector protein translocation into host cells.

03

Biological functions

Protein translocationBacterial virulenceHost-pathogen interactionEffector protein delivery
04

Disease associations

InfectionGastroenteritisPneumoniaPlagueSepticemia
05

Safety considerations

Potential for off-target effects on evolutionarily related flagellar systemsChallenges in achieving sufficient concentration at the infection siteNeed for narrow-spectrum specificity to preserve the host microbiome
06

Interacting drugs

Salicylidene acylhydrazides

6 more in the full profile.

07

Biomarkers

Secreted effector proteins (e.g., SopB, IpaB)V-antigen (LcrV)Needle tip proteins (PcrV, IpaD)

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