The satF (sat) Virulence Gene in E. coli
The sat gene encodes Secreted Autotransporter Toxin (Sat), a 107-kDa serine protease that functions as a significant virulence factor in uropathogenic and enteroaggregative E. coli strains by disrupting epithelial cell integrity through cytoskeletal damage and tight junction disruption, requiring standard antimicrobial therapy guided by susceptibility testing when these strains cause clinical infection.
Molecular Characteristics and Mechanism of Action
Sat is a serine protease autotransporter of Enterobacteriaceae (SPATE) with distinct structural features 1:
- Contains a 49 amino acid signal sequence, a 107-kDa passenger domain with serine protease active site (GDSGSG motif), and a 30-kDa C-terminal autotransporter domain 1
- The serine at position 256 (S256) is the catalytically active residue essential for all cytotoxic effects 2
- Functions as an active serine protease that is secreted and released into the extracellular environment 1
Pathogenic Mechanisms
Sat induces multiple forms of cellular damage through direct proteolytic activity 2:
Cellular Entry and Cytoskeletal Effects
- Sat is internalized by host cells and localizes to the cytoskeletal fraction 2
- Causes F-actin disruption leading to cell detachment in infected cells 3
- Mediates cytoskeletal contraction and actin loss in bladder and kidney epithelial cells 2
- Induces cell rounding in bladder cells and elongation in kidney cells 2
Tight Junction Disruption
- Promotes lesions in tight junctions of polarized epithelial cells by causing rearrangements of ZO-1, ZO-3, and occludin proteins 4
- Increases paracellular permeability without necessarily affecting transepithelial electrical resistance 4
- This serine protease-dependent disassembly facilitates bacterial invasion and systemic spread 4
Protein Degradation
- Degrades specific membrane/cytoskeletal proteins including fodrin and leukocyte function-associated molecule 1 2
- Cleaves nuclear proteins including microtubule-associated proteins, LIM domain-only protein 7, and poly(ADP-ribose) polymerase 2
Clinical Associations and Epidemiology
The sat gene shows strong association with pathogenic E. coli strains across multiple infection sites:
Uropathogenic E. coli (UPEC)
- Significantly more prevalent in strains causing acute pyelonephritis compared to fecal commensal strains (p=0.029) 1
- Found in 88% of UTI-associated Afa/Dr diffusely adhering E. coli (DAEC) strains 4
- Elicits strong antibody response during urinary tract infection 1
Enteroaggregative E. coli (EAEC)
- Detected in 93.7% of EAEC supernatants from sat-positive strains 3
- Present in 46% of strains from children with diarrhea versus only 16% from asymptomatic children 4
- Induces intense cell detachment during EAEC infection of polarized intestinal cells 3
Extraintestinal Infections
- Identified in E. coli strains isolated from neonatal septicemia and meningitis 3
- Endothelial cells (HUVEC) show greater sensitivity to Sat than urinary or intestinal tract cells, suggesting a role in bloodstream infections 3
Clinical Management Approach
Diagnostic Considerations
- Suspect sat-positive strains in severe or invasive E. coli infections, particularly pyelonephritis, EAEC diarrhea with severe symptoms, or bloodstream infections 3, 1, 4
- Standard culture and susceptibility testing remains the cornerstone; sat detection is not routinely performed but may be available in research settings 3
Antimicrobial Treatment
- Treat according to standard antimicrobial susceptibility patterns for the isolated E. coli strain, as sat presence does not alter antibiotic susceptibility 1
- For pyelonephritis with sat-positive UPEC: use fluoroquinolones, third-generation cephalosporins, or other agents based on local resistance patterns 1
- For EAEC diarrhea: consider antimicrobial therapy in severe cases with evidence of invasive disease 3, 4
Important Clinical Caveat
The presence of sat does not universally indicate virulence - the probiotic E. coli Nissle 1917 contains a functional sat gene but does not cause disease, as other secreted factors provide protective effects against Sat-mediated barrier disruption 5. This demonstrates that sat expression requires additional pathotype-specific genetic determinants to function as a virulence factor 5.