The Escherichia coli Type III Secretion System 2 Has a Global Effect on Cell Surface

Area of Science:

• Microbiology
• Pathogenesis
• Bacterial Genetics

Background:

• Extraintestinal pathogenic Escherichia coli (ExPEC) are significant causes of urinary tract infections and septicemia, often exhibiting antibiotic resistance.
• The ETT2 pathogenicity island (PAI) is present in many ExPEC strains and was initially presumed to encode a type III secretion system (T3SS) similar to Salmonella SPI-1.
• Understanding ExPEC virulence factors is critical for developing new antibacterial drugs and vaccines.

Purpose of the Study:

• To investigate the actual function of the ETT2 pathogenicity island in E. coli serotype O2, particularly its role in secretion and pathogenicity.
• To determine the impact of ETT2 on bacterial surface characteristics, motility, and resistance to host defense mechanisms.

Main Methods:

• Proteomic analysis of secreted proteins in E. coli strains with and without an intact ETT2 gene cluster.
• Construction and analysis of ETT2 deletion mutants to assess effects on gene transcription, protein secretion, motility, and resistance.
• Evaluation of mutant sensitivity to serum, detergents, and antibiotics.

Main Results:

• Contrary to expectations, ETT2 does not encode a functional T3SS for effector injection; secreted proteins are primarily flagellar.
• Deletion of ETT2 significantly reduces flagellar protein secretion and gene transcription, impairing motility.
• ETT2 deletion alters fimbrial and cell surface protein secretion, increases outer membrane vesicle (OMV) production, confers resistance to detergents and novobiocin, and crucially, renders bacteria sensitive to serum.

Conclusions:

• The ETT2 gene cluster plays a global role in E. coli cell surface architecture and physiology, rather than acting as a canonical T3SS.
• ETT2 is essential for serum resistance, a key factor in ExPEC septicemia pathogenesis.
• ETT2 represents a potential target for novel therapeutic strategies against ExPEC infections.