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Step 1 · Microbiology

Gram-Positive Rods

Toxins, spores, and buzzwords from tetanus to diphtheria

Microbiology·Bacteriology·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy
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Overview: the roster and the spore-formers

Few rods matter. The high-yield gram-positive rods are Clostridium, Bacillus, Listeria, and Corynebacterium (plus Gardnerella, a gram-variable rod behind bacterial vaginosis). Nearly every question reduces to matching an exposure to a toxin mechanism.

Spores. Clostridium and Bacillus form spores: dormant, dehydrated forms with a dipicolinic acid core and a keratin-like coat that resist heat, drying, and most disinfectants. Spores explain soil-borne tetanus, infant botulism from honey, and B. cereus surviving the cooking of rice.

The gram-positive rod roster
GenusOxygenSporesSignature
ClostridiumObligate anaerobeYesToxin-driven: tetanus, botulism, gas gangrene, C. difficile colitis
BacillusAerobeYesAnthrax; B. cereus food poisoning
ListeriaFacultative anaerobe; facultative intracellularNoCold growth, actin rockets, meningitis at the extremes of age
CorynebacteriumAerobic or facultativeNoDiphtheria: pseudomembrane, EF-2 toxin

Clostridial neurotoxins: tetanus and botulism

Shared mechanism, opposite result. Both toxins are proteases that cleave SNARE proteins and block neurotransmitter release. What differs is the neuron they reach, so one causes rigidity and the other floppiness.

Tetanus. C. tetani enters through a wound contaminated with soil (the classic rusty nail). Tetanospasmin travels retrogradely up axons to the spinal cord, where it blocks release of the inhibitory transmitters GABA and glycine from Renshaw cells. Unopposed motor firing produces spastic paralysis: trismus (lockjaw), risus sardonicus, and opisthotonus. Management combines human tetanus immune globulin, toxoid vaccination, benzodiazepines for spasms, and wound debridement.

Botulism. Botulinum toxin blocks ACh release at the neuromuscular junction, causing a symmetric descending flaccid paralysis that begins with cranial nerves: ptosis and the 4 Ds (diplopia, dysphagia, dysarthria, dysphonia). Adults ingest preformed toxin in canned or home-preserved food; infants ingest spores (classically in honey) that germinate and make toxin in the gut, producing a constipated, floppy baby. Treatment is antitoxin.

Tetanus vs botulism
FeatureTetanospasminBotulinum toxin
SiteSpinal inhibitory interneurons (Renshaw cells)Neuromuscular junction
Transmitter blockedGABA and glycineAcetylcholine
ParalysisSpastic: lockjaw, risus sardonicus, opisthotonusFlaccid, descending: ptosis, diplopia, dysphagia
SourceWound contaminated with soilPreformed toxin in canned food (adults); spores in honey (infants)

Clostridia of tissue and gut

C. perfringens. Its alpha toxin is a lecithinase (phospholipase C) that degrades cell membranes, causing myonecrosis (gas gangrene, with crepitus) and hemolysis; colonies show a double zone of hemolysis. It also causes a late-onset (10–12 hours) watery food poisoning from reheated meat dishes.

C. difficile. Toxin A is an enterotoxin, and toxin B is a cytotoxin that depolymerizes actin, killing enterocytes and forming the yellow plaques of pseudomembranous colitis. Classic triggers are clindamycin, ampicillin, cephalosporins, and fluoroquinolones; proton pump inhibitors add risk.

  1. Broad-spectrum antibioticClindamycin, ampicillin, cephalosporin, fluoroquinolone
  2. Normal flora wiped outC. difficile overgrows
  3. Toxins A and BEnterotoxin plus actin-disrupting cytotoxin
  4. Pseudomembranous colitisWatery diarrhea, abdominal pain, yellow plaques
How antibiotics trigger C. difficile

Diagnose by stool PCR or toxin EIA. Treat an initial episode with oral vancomycin or fidaxomicin (current guidelines favor these over metronidazole); recurrent disease may need fecal microbiota transplant.

Bacillus: anthrax and B. cereus

B. anthracis. Large gram-positive rods in chains; the only bacterium with a polypeptide capsule (poly-D-glutamate). Its toxin has three parts: protective antigen (binds and enters cells), edema factor (an adenylate cyclase that raises cAMP), and lethal factor (a protease).

  • Cutaneous anthrax: painless papule that becomes a black necrotic eschar, typically after handling animal hides or wool.
  • Inhalational anthrax (woolsorter disease): inhaled spores cause flu-like illness, then hemorrhagic mediastinitis with a widened mediastinum and shock.

B. cereus. Spores survive cooking, and rice left at room temperature lets them germinate. Two syndromes follow: an emetic syndrome 1–5 hours after reheated fried rice, caused by preformed, heat-stable cereulide, and a watery diarrheal syndrome at 8–18 hours from a heat-labile enterotoxin.

Toxin-mediated food poisoning by onset
OrganismTypical foodOnsetMain effect
B. cereus (emetic)Reheated fried rice1–5 hoursVomiting (preformed cereulide)
S. aureus (contrast)Mayonnaise, meats, dairy2–6 hoursVomiting (preformed enterotoxin)
B. cereus (diarrheal)Varied foods8–18 hoursWatery diarrhea (heat-labile toxin)
C. perfringensReheated meat10–12 hoursWatery diarrhea
C. botulinumHome-canned foodTypically 12–36 hoursDescending flaccid paralysis

Listeria and Corynebacterium

Listeria monocytogenes. A facultative intracellular rod that is catalase-positive, beta-hemolytic, shows tumbling motility, and grows at refrigerator temperatures. Sources are unpasteurized dairy, soft cheeses, and deli meats. It polymerizes host actin into "rockets" (comet tails) that push it directly into neighboring cells, so it never enters the extracellular space where antibody could bind; cell-mediated immunity controls it.

Listeria disease. Infection in pregnancy spreads transplacentally, causing amnionitis, fetal loss, or granulomatosis infantiseptica; neonates can also acquire it in the birth canal and develop meningitis. Meningitis also strikes the elderly and immunocompromised, while healthy adults get self-limited febrile gastroenteritis. Treat with ampicillin; it is added to empiric meningitis coverage in neonates and older adults because cephalosporins do not cover Listeria.

Corynebacterium diphtheriae. Club-shaped rods with metachromatic (volutin) granules arranged in "Chinese letters." Culture on Löffler medium or tellurite agar, and confirm toxin production with the Elek test. Disease: a gray pharyngeal pseudomembrane that bleeds if scraped, "bull neck" cervical lymphadenopathy, and toxin-mediated myocarditis and arrhythmias. Treat with antitoxin plus penicillin or erythromycin; prevent with the toxoid (DTaP).

  1. Lysogenic β-prophageCarries the tox gene; only phage-infected strains are toxigenic
  2. Toxin ADP-ribosylates EF-2Same mechanism as Pseudomonas exotoxin A
  3. Protein synthesis haltsHost cells die
  4. Pseudomembrane, myocarditisGray membrane, bull neck, arrhythmias
Diphtheria toxin action

Toxin shortcuts: tetanus blocks GABA/glycine (spastic); botulinum blocks ACh (flaccid); perfringens alpha toxin is a lecithinase; C. difficile toxin B depolymerizes actin; anthrax edema factor is an adenylate cyclase; diphtheria toxin and Pseudomonas exotoxin A ADP-ribosylate EF-2.