Sat vs SatF Virulence Genes in E. coli
Critical Clarification
The provided evidence discusses only the sat gene and its protein product (Sat), with no mention of a distinct "satF" gene. Based on available research, satF does not appear to be a recognized separate virulence gene in E. coli literature. The question may reflect confusion about nomenclature or refer to variants/alleles of the sat gene itself.
The Sat Virulence Gene
Gene Identity and Function
Sat (secreted autotransporter toxin) is a 107-kDa serine protease autotransporter encoded by a 3885 bp gene producing a 142 kDa precursor protein 1
The protein belongs to the SPATE (Serine Protease Autotransporters of Enterobacteriaceae) family with three characteristic domains: a 49 amino acid signal sequence, a 107 kDa passenger domain with serine protease activity (GDSGSG consensus site), and a 30 kDa C-terminal autotransporter domain 1
Clinical Significance and Pathogenic Role
Sat functions as a major virulence factor in extraintestinal pathogenic E. coli (ExPEC), particularly in bloodstream infections and urinary tract infections, through both direct cytotoxic effects and immune system evasion. 2
Cytotoxic Mechanisms:
Vacuolating cytotoxin activity on bladder (CRL-1749) and kidney (CRL-1573) epithelial cells, causing cell elongation, loosening of cellular junctions, and significant cytoplasmic vacuolation 3
F-actin disruption leading to cell detachment in polarized intestinal cells during enteroaggregative E. coli (EAEC) infection 4
Differential tissue sensitivity: Endothelial cells (HUVEC) show greater sensitivity to Sat than urinary or intestinal tract cells, suggesting enhanced virulence potential in bloodstream infections 4
Immune Evasion Properties:
Cleaves multiple complement system proteins (all tested substrates except C1q) in a dose- and time-dependent manner, affecting all three complement pathways 2
Confers serum resistance: E. coli strains producing Sat survive in normal human serum, and even non-pathogenic E. coli DH5α survives in serum pre-incubated with Sat 2
Reduces mortality in sepsis models by 50% when sat is knocked out, demonstrating critical role in bloodstream infection establishment 2
Epidemiology and Distribution
Highly prevalent in uropathogenic E. coli (UPEC): Significantly more common in strains causing acute pyelonephritis compared to fecal commensal strains (P = 0.029) 1
Detected in 93.7% of EAEC strains harboring the sat gene 4
Found in 34.8% of ECOR collection strains from healthy human stools, with high prevalence in phylogenetic groups D and B2 (associated with extraintestinal infections) 5
Present in neonatal septicemia and meningitis isolates 4
Pathological Evidence
In vivo kidney damage: Murine urinary tract infection models show dissolution of glomerular membranes and vacuolation of proximal tubule cells in wild-type CFT073 infections, but not with sat mutants 3
No effect on colonization: Sat is not required for intestinal colonization, and sat mutants actually outcompete wild-type strains in streptomycin-treated mouse models 5
Context-Dependent Virulence
A critical caveat: Sat does not universally function as a virulence factor across all E. coli strains. In the probiotic E. coli Nissle 1917 (EcN), despite sat expression and active serine protease secretion, the protein does not cause pathogenic effects 5. EcN secretes other factors that protect against Sat-mediated barrier disruption, demonstrating that virulence depends on the complete genetic background of the pathotype, not sat alone 5.
Clinical Management Implications
Sat presence indicates enhanced pathogenic potential in ExPEC strains, particularly for bloodstream and urinary tract infections requiring more aggressive antimicrobial therapy
Elicits strong antibody responses during infection, as demonstrated in murine models 1
Consider Sat-producing strains as higher risk for severe complications including sepsis, given the 50% mortality difference in animal models 2