Escherichia coli
Gram-negative facultative anaerobic rod; dominant commensal coliform and globally critical pathogen. Six intestinal pathotypes use distinct virulence strategies: ETEC secretes heat-labile (LT) and heat-stable (ST) enterotoxins; EPEC/EHEC inject type III effectors via the LEE-encoded T3SS; EHEC additionally produces Shiga toxin (Stx1/Stx2), a ribosome-inactivating toxin that binds Gb3 receptors and cleaves 28S rRNA to destroy glomerular endothelium, causing haemolytic uraemic syndrome (HUS) in 5–15% of infected children; EIEC invades colonic cells like Shigella. ExPEC (extraintestinal pathogenic E. coli) causes 80–85% of community UTIs (UPEC) — via FimH-uroplakin binding, intracellular bacterial community formation, and siderophore-mediated iron acquisition — neonatal meningitis (K1 capsule strains), and Gram-negative bacteraemia. LPS lipid A is the archetypal TLR4 agonist and endotoxin; CTX-M ESBLs and NDM/KPC carbapenemases make drug-resistant E. coli a leading global AMR threat.
Classification & Structure
| Gram stain | Gram-negative; thin peptidoglycan in periplasm; outer membrane with LPS on outer leaflet; β-barrel porins (OmpA, OmpC, OmpF) permit hydrophilic antibiotic entry — also site of β-lactamase action (CTX-M ESBL, KPC in periplasm) |
| Morphology | Straight rods, 1.0–2.0 µm × 0.4–0.7 µm; peritrichous flagella (H antigen); type 1 fimbriae (FimH) and P fimbriae (PapG) for adhesion; O-antigen capsule (K antigen) in invasive strains; LPS O-antigen (serotype determinant) |
| Motility | Peritrichous flagella (H antigens H1, H7, etc.); motile in liquid media; UPEC downregulates flagellin expression during bladder colonisation (phase variation — immune evasion of TLR5) |
| Toxins | LT (heat-labile enterotoxin; ADP-ribosylates Gsα → ↑cAMP → Cl³ secretion; ETEC); ST (heat-stable toxin; activates guanylate cyclase → ↑cGMP; ETEC); Stx1/Stx2 (Shiga toxin; ribosome-inactivating N-glycosidase; EHEC; phage-encoded) |
| Spores | None. E. coli does not form spores. Resistance to environmental stress is mediated by biofilm formation (intracellular bacterial communities in bladder) and plasmid-encoded resistance genes. |
Pathogenesis
1 · ETEC enterotoxins — secretory diarrhoea
Enterotoxigenic E. coli (ETEC) colonises the small intestine via colonisation factor antigens (CFA/CS fimbriae) and secretes LT and/or ST. LT (structurally and mechanistically homologous to cholera toxin) ADP-ribosylates the Gαs subunit of adenylyl cyclase → constitutive ↑cAMP → CFTR-mediated Cl³ secretion without Na³ co-absorption → massive secretory watery diarrhoea. ST activates guanylyl cyclase C (GC-C) on enterocytes → ↑cGMP → PKG-II → CFTR activation and NHE3 inhibition. Together: the leading cause of traveller's diarrhoea (80% of cases) and a major killer of children in developing countries.
2 · EHEC T3SS and Shiga toxin — haemolytic uraemic syndrome
Enterohaemorrhagic E. coli (EHEC O157:H7) uses the LEE-encoded type III secretion system (T3SS) to inject Tir, Map, EspF, and other effectors into enterocytes. Tir inserts into the host membrane as the receptor for intimin (bacterial outer membrane adhesin) → attaching and effacing (A/E) lesion with F-actin pedestals. Shiga toxin 2 (Stx2; more potent than Stx1 for HUS) is released from the gut and enters the bloodstream, where its B-subunit pentamer binds Gb3 (globotriaosylceramide) on glomerular endothelium (high Gb3 expression), brain neurons, and renal tubular cells. A-subunit N-glycosidase cleaves adenine from 28S rRNA of the 60S ribosomal subunit → irreversible ribosome inactivation → cell death → microangiopathic haemolytic anaemia + thrombocytopenia + acute renal failure = HUS triad (5–15% of EHEC infections; more common in children <5 years).
3 · UPEC intracellular bacterial communities — recurrent UTI
Uropathogenic E. coli (UPEC) ascends the urethra, attaches to bladder urothelium via FimH (type 1 fimbrial tip adhesin) binding mannosylated uroplakin receptors (UPIa/Ib) on umbrella cells, and invades the umbrella cell cytoplasm. Inside the cytoplasm, UPEC forms intracellular bacterial communities (IBCs) — densely packed biofilm-like structures of 10²–10⁴ bacteria protected from antibiotics and neutrophil killing. IBCs can persist as quiescent intracellular reservoirs (QIRs) for months after clinical resolution, explaining the 25–50% recurrence rate of UTI. P fimbriae (PapG adhesin; binds Galα1-4Gal glycolipids on uroepithelium) mediate ascent to the renal pelvis in pyelonephritis.
4 · LPS endotoxin — TLR4 activation and septic shock
E. coli lipopolysaccharide (LPS) is the archetypal TLR4 agonist. Lipid A (the membrane-anchored moiety) is transferred by LBP (LPS-binding protein) to CD14, then presented to the TLR4/MD-2 heterodimer. Downstream signalling via MyD88 → NF-κB (TNF-α, IL-1β, IL-6, IL-8) and TRIF → IRF3 (IFN-β). At physiological concentrations: beneficial local inflammation and neutrophil recruitment. At pathological concentrations (Gram-negative bacteraemia, especially with antibiotic lysis): cytokine storm → systemic endothelial injury → distributive shock, DIC, multi-organ failure. Kupffer cells in the liver activate via TLR4 → TNF-α / IL-1β → hepatocyte apoptosis via TNFR1/caspase-8 (contributing to acute liver injury and elevated transaminases in Gram-negative sepsis).
5 · UPEC immune evasion — phase variation and K1 capsule
UPEC employs multiple immune evasion strategies: (i) Type 1 fimbriae undergo phase variation (fim switch inversion) — downregulated during intracellular IBC phase to reduce TLR4/flagellin sensing; (ii) K capsule polysaccharides impair complement deposition (C3b) and opsonophagocytosis — K1 polysialic acid mimics human neural cell adhesion molecule (NCAM), reducing anti-K1 antibody cross-reactivity; (iii) Siderophores (aerobactin, enterobactin, salmochelin, yersiniabactin) scavenge iron from the iron-limited urinary/blood environment, an essential virulence determinant; (iv) Serum resistance via TraT (outer membrane protein inhibiting C5b-9 MAC assembly) and O-antigen length reducing complement access to the membrane.
6 · ESBL / CRE resistance — the AMR crisis
E. coli is the dominant global vehicle for CTX-M extended-spectrum β-lactamases (ESBLs) — plasmid-encoded enzymes hydrolysing all penicillins and 3rd-generation cephalosporins. CTX-M-15 is now present in 15–30% of community E. coli UTI isolates in many countries. KPC and NDM carbapenemases (also plasmid-encoded) hydrolyse carbapenems, leaving only colistin, fosfomycin, tigecycline, and novel combinations (ceftazidime-avibactam, meropenem-vaborbactam) active. MCR-1 plasmid colistin resistance, combined with NDM carbapenemase, creates near-pandrug-resistant strains. Fluoroquinolone resistance (gyrA/parC mutations + qnr plasmid genes) is now common globally, limiting empirical UTI treatment.
Host Immune Response
Disease Spectrum
| Presentation | Severity | At-Risk Groups | Mortality |
|---|---|---|---|
| Uncomplicated UTI (UPEC) | Dysuria, frequency, suprapubic pain; pyuria; nitrite-positive dipstick; >10⁵ CFU/mL E. coli in midstream urine | Women (50× higher incidence than men due to short urethra); sexually active; post-menopausal (↓oestrogen → ↓vaginal Lactobacillus) | Excellent; 3–7 d nitrofurantoin or TMP-SMX |
| Pyelonephritis (UPEC) | Fever, rigors, loin pain, CVA tenderness; bacteraemia in 20–30%; urosepsis in elderly | Women; urinary tract abnormalities; diabetes; pregnancy; elderly | 1–5% |
| Traveller's diarrhoea (ETEC) | Watery diarrhoea; 12–72h post-exposure; self-limited 3–5 days; dehydration risk in infants and elderly | Travellers to developing countries; infants in low-income settings | <1% (adults); higher in malnourished infants |
| Haemorrhagic colitis (EHEC O157:H7) | Watery diarrhoea → bloody (haemorrhagic) colitis; severe cramping; low-grade fever or afebrile; onset 3–4 days post-ingestion; onset from undercooked beef, spinach, sprouts | Children <5 years; elderly; immunocompromised | <1% (uncomplicated); 3–5% if HUS develops |
| HUS (Shiga toxin) | Microangiopathic haemolytic anaemia + thrombocytopenia + acute kidney injury (HUS triad); 7–10 days post-diarrhoea onset; requires renal replacement therapy in 50–70% of HUS cases; neurological complications (seizures, stroke) in 25% | Children <5 years (highest HUS conversion rate); elderly | 3–5% acute; 25% long-term CKD |
| Neonatal meningitis (NMEC K1) | Fever, bulging fontanelle, seizures; CSF >1,000 WBC; E. coli K1 PCR/culture; devastating neuroinflammation | Neonates (first 28 days); premature infants; GBS-negative mothers (E. coli ranks 2nd) | 15–40% acute; >30% neurological sequelae |
| Gram-negative bacteraemia / septic shock | Fever or hypothermia; tachycardia; hypotension; positive blood cultures; source: urinary/biliary/GI/lung; ESBL/CRE strains dramatically narrow treatment options | Elderly; immunocompromised; hospital-acquired; cirrhosis (SBP) | 20–30% (sensitive); 40–60% (CRE strains) |
Treatment & Prophylaxis
| Uncomplicated UTI (sensitive) | Nitrofurantoin 100 mg MR twice daily × 5 days (bladder-only infections; not pyelonephritis); trimethoprim-sulfamethoxazole (TMP-SMX) DS twice daily × 3 days (if local resistance <20%); pivmecillinam 400 mg twice daily × 5 days (Europe; excellent bladder UTI activity); fosfomycin 3 g sachet single dose. |
| Pyelonephritis (sensitive) | Oral ciprofloxacin 500 mg twice daily × 7 days or TMP-SMX DS twice daily × 14 days; severe/ESBL: IV ertapenem or meropenem until sensitivities available; IV ceftriaxone as empirical option if local ESBL prevalence <15%. |
| ESBL-producing E. coli | Ertapenem (IV/IM) for serious infections; meropenem for critically ill; fosfomycin or pivmecillinam for uncomplicated lower UTI only; carbapenems are gold standard for systemic ESBL infections; avoid cephalosporins (hydrolysed by CTX-M). |
| Carbapenem-resistant E. coli (CRE/NDM) | Ceftazidime-avibactam (KPC, OXA-48); meropenem-vaborbactam (KPC); aztreonam-avibactam (MBL/NDM; only combination active against NDM); cefiderocol (siderophore cephalosporin); combination therapy for extensively resistant strains; infectious disease specialist consultation essential. |
| EHEC (no antibiotics) | Antibiotics are contraindicated in confirmed EHEC haemorrhagic colitis — they trigger Stx2 phage induction → ↑Shiga toxin release → ↑HUS risk (meta-analysis); supportive care: IV fluids, avoid NSAIDs/anti-motility agents; renal replacement if AKI develops; eculizumab (anti-C5) used in severe HUS cases at specialist centres. |
| Vaccine (in development) | No FDA-approved E. coli vaccine for human use. FimH vaccine (anti-type 1 fimbria tip adhesin) in Phase II trials for UPEC recurrent UTI prevention; ETEC vaccines (LT/CS-based) in development for traveller's diarrhoea; Stx-based HUS vaccine candidates in preclinical development. |
Connections
References
- Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2(2):123-40. doi:10.1038/nrmicro818 · PubMed 15040260
- Croxen MA, Finlay BB. Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol. 2010;8(1):26-38. doi:10.1038/nrmicro2265 · PubMed 19966814
- Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014;28(1):1-13. doi:10.1016/j.idc.2013.09.003 · PubMed 24484571
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073-86. doi:10.1016/S0140-6736(05)71144-2 · PubMed 15781103
- WHO. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022. who.int
Contribute to the Pathogen Atlas
This entry covers the major E. coli pathotypes, Shiga toxin biology, UPEC intracellular communities, and AMR. Planned expansions include ETEC vaccine pipeline, structural biology of FimH–uroplakin interaction, and ESBL epidemiology by region. Every entry follows the same schema: structured frontmatter, peer-reviewed citations, and cross-atlas links.