E. coli Pathotypes, Klebsiella, Proteus & Yersinia
One family of gut rods, many distinct virulence strategies
Enterobacterales: shared features
Family traits. Enterobacterales are facultatively anaerobic gram-negative rods that are oxidase-negative, ferment glucose, and reduce nitrate to nitrite. The last property is the basis of the urine dipstick nitrite test: a positive result implies an enteric gram-negative uropathogen, whereas Enterococcus and S. saprophyticus, which do not reduce nitrate, give nitrite-negative infections. All carry lipopolysaccharide endotoxin in the outer membrane.
Lactose fermentation. On MacConkey agar, lactose fermenters (E. coli, Klebsiella, Enterobacter, Citrobacter) form pink colonies, and E. coli shows a green metallic sheen on eosin methylene blue agar. Proteus and Yersinia are non-fermenters and form colorless colonies.
E. coli pathotypes
Uropathogenic E. coli (UPEC). The leading cause of both cystitis and pyelonephritis. Type 1 fimbriae bind the bladder mucosa, and P fimbriae bind Gal-Gal glycolipids of the P blood group antigen on uroepithelium, allowing ascent to the kidney.
K1 capsule. K1-encapsulated E. coli is, with group B Streptococcus, a leading cause of neonatal sepsis and meningitis. The capsule is polysialic acid, identical to the N. meningitidis serogroup B capsule, which makes it poorly immunogenic and antiphagocytic.
| Pathotype | Key virulence mechanism | Setting | Stool |
|---|---|---|---|
| ETEC | Heat-labile toxin ADP-ribosylates Gs (↑cAMP); heat-stable toxin activates guanylate cyclase (↑cGMP); no invasion | Traveler's diarrhea; children in low-resource regions | Watery, no blood or fever |
| EPEC | Bundle-forming pili and intimin create attaching-effacing lesions with actin pedestals; no toxin | Infants, low-resource settings | Watery (malabsorptive) |
| EIEC | Plasmid-encoded invasion of colonic epithelium, cell-to-cell spread; no Shiga toxin | Food and water outbreaks | Febrile dysentery with fecal leukocytes |
| EHEC O157:H7 | Phage-encoded Shiga-like toxin inactivates 60S ribosome | Undercooked ground beef, unpasteurized juice, produce, petting zoos | Bloody, little or no fever; HUS risk |
ETEC toxins. The heat-labile toxin behaves like cholera toxin, locking Gs on; the heat-stable toxin binds guanylate cyclase C. Both drive chloride and water secretion from the small bowel without mucosal damage.
EHEC and HUS. Shiga-like toxin removes an adenine from 28S rRNA of the 60S subunit, stopping protein synthesis. Absorbed toxin injures endothelium, particularly in glomerular capillaries, producing platelet microthrombi and hemolytic uremic syndrome: microangiopathic hemolytic anemia with schistocytes, thrombocytopenia, and acute kidney injury, typically about a week after the diarrhea in young children. Unlike most E. coli, O157:H7 does not ferment sorbitol, so it forms colorless colonies on sorbitol-MacConkey agar; a Shiga toxin assay also detects non-O157 strains.
In suspected EHEC infection avoid antibiotics and antimotility agents, which may increase toxin release or retention and the risk of HUS; management is supportive.
Klebsiella pneumoniae
Organism. A nonmotile, lactose-fermenting, urease-positive rod whose thick polysaccharide capsule produces very mucoid colonies and blocks phagocytosis.
Pneumonia. People prone to aspiration, especially those with alcohol use disorder or diabetes, develop lobar pneumonia, often of an upper lobe, with thick bloody currant-jelly sputum. Tissue necrosis leads to cavitation and lung abscess; the heavy exudate can expand the lobe enough to bow the adjacent fissure on chest radiograph.
Hypervirulent strains. Hypermucoviscous strains (often capsular types K1 or K2) cause community-acquired pyogenic liver abscess in otherwise healthy or diabetic adults, especially in East Asia, and can spread to the eye (endophthalmitis) and meninges. Hypermucoviscosity is demonstrated by the string test, in which a loop lifted from a colony draws a string longer than 5 mm.
Hospital infections and resistance. Classic strains cause catheter-associated UTIs, ventilator-associated pneumonia, and bacteremia. Klebsiella is intrinsically resistant to ampicillin through a chromosomal penicillinase, and it is the prototypic carrier of acquired extended-spectrum β-lactamases and of the K. pneumoniae carbapenemase (KPC).
| Enzyme | Typical organisms | Drugs destroyed | Preferred therapy |
|---|---|---|---|
| ESBL | Klebsiella, E. coli (plasmid) | Penicillins, third-generation cephalosporins, aztreonam | Carbapenem |
| Inducible AmpC | Enterobacter, Citrobacter freundii, Serratia (chromosomal) | Third-generation cephalosporins after derepression | Cefepime or carbapenem |
| KPC | Klebsiella and other Enterobacterales (plasmid) | Nearly all β-lactams including carbapenems | Ceftazidime-avibactam or meropenem-vaborbactam |
Proteus, Serratia and AmpC organisms
Proteus mirabilis. A highly motile, lactose-nonfermenting rod whose colonies spread across agar in waves (swarming motility). Its urease splits urea into ammonia and carbon dioxide, alkalinizing the urine (pH often above 7) and precipitating struvite, magnesium ammonium phosphate. Struvite can grow into a staghorn calculus that fills the renal pelvis and calyces; the stone harbors bacteria, so cure usually requires complete stone removal along with antibiotics. The ammonia also gives the urine a pungent odor.
Serratia marcescens. A motile organism that may form red-pigmented colonies (prodigiosin) and causes nosocomial UTIs, pneumonia, and catheter-related bacteremia. As a catalase-positive organism it is among the pathogens that recur in chronic granulomatous disease, along with S. aureus, Nocardia, Burkholderia cepacia, and Aspergillus. Proteus and Serratia are intrinsically resistant to polymyxins.
Inducible AmpC. Enterobacter, Citrobacter freundii, and Serratia carry a chromosomal AmpC β-lactamase that is normally repressed. During third-generation cephalosporin therapy, mutants that produce it constantly can be selected, so an infection that first tested susceptible may relapse with resistance. Cefepime, which is more stable to AmpC, or a carbapenem is used for serious infections.
Yersinia enterocolitica
Exposure. Sources include undercooked pork (classically chitterlings prepared at home), unpasteurized milk, contaminated water, and pet feces, especially from puppies.
Cold growth and iron. The organism multiplies at refrigerator temperature, so it can proliferate in stored red cell units and cause transfusion-associated septic shock. Iron overload (hemochromatosis, transfused thalassemia) and deferoxamine therapy predispose to severe infection, because Yersinia can use deferoxamine-bound iron as a siderophore.
Clinical picture. After ingestion, Yersinia invades Peyer patches and drains to mesenteric nodes. Fever, diarrhea (sometimes bloody), and right lower quadrant pain from terminal ileitis and mesenteric adenitis produce pseudoappendicitis. Post-infectious complications include reactive arthritis (HLA-B27 associated) and erythema nodosum. Enteritis is usually self-limited; bacteremia or severe disease in iron-overloaded or immunocompromised hosts is treated with antibiotics such as a fluoroquinolone or TMP-SMX.
Right lower quadrant pain with a normal appendix, an inflamed terminal ileum, and enlarged mesenteric nodes, especially in a patient receiving deferoxamine, points to Yersinia.