Gram-Negative Enterics & Others

Overview: enterics and the MacConkey plate

Enterobacteriaceae. The enteric gram-negative rods ferment glucose, reduce nitrate, and are oxidase-negative. The curved and non-enteric rods in this chapter (Pseudomonas, Vibrio, Campylobacter, H. pylori) are instead oxidase-positive.

Lactose fermentation. On MacConkey agar, lactose fermenters produce acid and grow as pink colonies; non-fermenters stay colorless.

• Fast fermenters (pink): Klebsiella, E. coli, Enterobacter (test with MacConKEE'S). E. coli also grows with a green metallic sheen on EMB agar.
• Non-fermenters (colorless): Salmonella, Shigella, Proteus, Pseudomonas, Yersinia.

E. coli and Klebsiella

E. coli. The leading cause of UTI and of gram-negative sepsis; strains with the K1 capsule cause neonatal meningitis. Each virulence factor maps to a disease: fimbriae → cystitis and pyelonephritis; K capsule → pneumonia and neonatal meningitis; LPS endotoxin → septic shock.

EHEC and hemolytic uremic syndrome. EHEC O157:H7 does NOT ferment sorbitol, so it forms colorless colonies on sorbitol-MacConkey agar. Its Shiga-like toxin inactivates the 60S ribosomal subunit and injures endothelium, especially in glomeruli.

Avoid antibiotics and antimotility agents in suspected EHEC: they increase toxin release and HUS risk, so treatment is supportive.

Klebsiella. A lactose fermenter with a huge mucoid capsule. It causes lobar pneumonia with thick, bloody "currant-jelly" sputum and lung abscesses. Remember the 4 As: Aspiration, Abscess, Alcoholics, diAbetics. It also causes UTIs.

Salmonella and Shigella

Shared features. Both are non-lactose fermenters that invade the gut mucosa, but they differ in almost everything else.

Typhoid fever. Salmonella typhi has a human-only reservoir and causes enteric fever: fever (often with relative bradycardia), abdominal pain, and rose spots on the abdomen. Constipation is typical early, and "pea-soup" diarrhea may develop. Chronic carriers harbor the organism in the gallbladder ("Typhoid Mary"). Treat with ceftriaxone or a fluoroquinolone; a vaccine exists. Nontyphoidal Salmonella causes gastroenteritis and classically osteomyelitis in sickle cell disease.

Shigella. Spreads fecal-orally, invades through M cells, and moves from cell to cell, producing dysentery. S. dysenteriae makes Shiga toxin, which, like the E. coli version, inactivates the 60S ribosome and can trigger HUS.

Oxidase-positive rods

Pseudomonas aeruginosa. An aerobic, oxidase-positive non-lactose fermenter with blue-green pigment (pyocyanin) and a grape-like odor; it thrives anywhere wet. Classic infections: burn wounds, pneumonia in cystic fibrosis and on ventilators, hot-tub folliculitis, malignant otitis externa in diabetics, osteomyelitis after a nail puncture through a shoe, and ecthyma gangrenosum, rapidly necrotic black skin lesions that signal bacteremia in neutropenic patients. Exotoxin A ADP-ribosylates EF-2, halting protein synthesis, the same mechanism as diphtheria toxin.

Helicobacter pylori. A curved, urease-positive, oxidase-positive rod. Urease makes ammonia that buffers gastric acid and is the basis of the urea breath test and rapid urease testing. It causes chronic gastritis, duodenal (and gastric) ulcers, gastric adenocarcinoma, and MALT lymphoma. Bismuth quadruple therapy (PPI, bismuth, metronidazole, tetracycline) is now preferred because clarithromycin resistance is common; clarithromycin triple therapy (PPI, clarithromycin, amoxicillin) is reserved for strains known to be susceptible.

Vibrio. V. cholerae is a comma-shaped, oxidase-positive rod that grows in alkaline media and spreads through contaminated water. Cholera toxin ADP-ribosylates Gs, locking adenylate cyclase on; cAMP drives massive chloride and water secretion into the lumen, producing painless, voluminous rice-water stools and rapid dehydration. Treatment is rehydration, ideally oral. V. vulnificus, from raw oysters, causes fulminant sepsis in patients with liver disease.

Campylobacter jejuni. A comma/S-shaped ("seagull") oxidase-positive rod that grows at 42 °C and is the most common cause of bacterial bloody diarrhea (poultry, unpasteurized milk, pets). Complications: Guillain-Barré syndrome (molecular mimicry) and reactive arthritis.

Endotoxin and toxin mechanisms

Endotoxin (LPS). Lipopolysaccharide of the gram-negative outer membrane, released when bacteria lyse; lipid A is the toxic part. It triggers three cascades:

• Macrophages (via CD14/TLR4): IL-1, IL-6, TNF-α → fever and hypotension.
• Complement: C3a (hypotension, edema) and C5a (neutrophil chemotaxis).
• Tissue factor: coagulation cascade → DIC.

Toxin mechanisms: cholera toxin and ETEC heat-labile toxin → Gs, raising cAMP; ETEC heat-stable toxin → cGMP; Shiga and Shiga-like toxins → 60S ribosome; Pseudomonas exotoxin A → EF-2.