Pathogenesis of E. coli Urinary Tract Infection
The pathogenesis of E. coli UTI involves bacterial colonization of the periurethral area, ascension to the bladder, attachment to uroepithelium via specialized adhesins, invasion of host cells, biofilm formation, and evasion of host immune responses.
Initial Colonization and Ascension
- E. coli, the most common causative agent of UTIs (accounting for approximately 75% of cases), initially colonizes the intestinal tract 1
- From the intestine, uropathogenic strains colonize the vaginal and periurethral areas 2
- Bacteria then ascend through the urethra to reach the bladder
- Risk factors that facilitate this process include:
- Female anatomy (shorter urethra)
- Sexual activity
- Use of spermicides or diaphragms
- Poor urinary hygiene
- Urinary retention or incomplete bladder emptying 1
Bacterial Attachment and Adhesion
- Attachment to uroepithelium is a critical virulence step that prevents bacteria from being washed away by urine flow 3
- Two primary types of adhesins are involved:
- Type 1 fimbriae - Recognize mannose-containing receptors in urinary slime, measured as mannose-sensitive hemagglutination 2
- P fimbriae (and other mannose-resistant adhesins) - Recognize globo-series glycolipids on epithelial cell surfaces, measured as mannose-resistant hemagglutination of human erythrocytes 3, 2
- P fimbriae are strongly associated with pyelonephritis and upper UTI, while type 1 fimbriae are more common in lower UTI 3
Invasion and Intracellular Persistence
- After attachment, UPEC can invade uroepithelial cells through endocytosis
- Inside cells, bacteria can:
- Form intracellular bacterial communities (IBCs)
- Establish quiescent intracellular reservoirs
- Evade host immune responses and antibiotic treatments
- Serve as a source for recurrent infections 4
Biofilm Formation
- UPEC can form biofilms on catheter surfaces and within the bladder
- Biofilms protect bacteria from:
- Host immune defenses
- Antibiotic penetration
- Environmental stresses
- This contributes to persistent and recurrent infections, particularly in catheterized patients 1
Virulence Factors
- Multiple virulence factors contribute to UPEC pathogenicity:
- Adhesins (P fimbriae, type 1 fimbriae, and other mannose-resistant adhesins)
- Toxins (hemolysin) - damage host cells and release nutrients
- Aerobactin system - iron acquisition system
- K capsule - prevents phagocytosis
- Serum resistance - protects against complement-mediated killing 3
- The more virulence factors a strain possesses, the more severe the infection it can cause 3
Host Response and Inflammation
- Bacterial attachment triggers host inflammatory responses
- Neutrophil recruitment leads to pyuria (hallmark of UTI)
- While inflammation helps clear infection, it can also cause tissue damage
- Host inflammatory response, rather than bacterial presence alone, contributes to renal scarring 1
Antibiotic Resistance Development
- UPEC strains increasingly demonstrate antimicrobial resistance
- Extended-spectrum β-lactamase (ESBL)-producing E. coli is becoming more common in community-acquired UTIs 5
- Phylogenetic group F has been associated with high rates of multidrug resistance 6
- Biofilm formation further contributes to antibiotic treatment failure 1
Clinical Implications
- Understanding this pathogenesis pathway helps guide treatment approaches:
Special Considerations
- In catheterized patients, the pathogenesis is modified as the catheter provides a direct route for bacterial entry and biofilm formation 1
- In complicated UTIs, structural or functional abnormalities of the urinary tract alter the pathogenesis and increase infection risk 1
- Recurrent UTIs may result from persistent intracellular bacterial reservoirs rather than reinfection from external sources 4
Understanding these pathogenic steps has implications for both treatment and prevention strategies for E. coli UTIs, particularly as antibiotic resistance continues to increase globally.