Notes
Clostridium
Sections
Rapid-growing
Thrive in anaerobic conditions, such as the intestinal tract, sewage, water, and soil.
Pathogenic strains produce histolytic toxins, enterotoxins, and neurotoxins.
Four strains that cause infection in humans:
Clostridium difficile causes diarrhea and colitis. Note: this bacterium has been renamed Clostridioides difficile
Clostridium perfringens causes gas gangrene and food poisoning.
Clostridium tetani causes tetanus.
Clostridium botulinum causes botulism.
Clostridium difficile
Transmitted via the fecal-oral route
Common colonizer of the human colon.
Historically associated with hospitalized patients, we've seen a rise in community-acquired cases.
A major cause of C. difficile infection is antibiotics that suppress the non-pathogenic colonic flora, which allows the opportunistic C. difficile to flourish.
Virulence factors:
Toxin A is an enterotoxin that attracts neutrophils, which release cytokines.
Toxin A also increases intestinal wall permeability by attacking colonic epithelial tight junctions.
Toxin B is a cytotoxin that acts on enterocyte actin to destroy cytoskeletal integrity.
Binary toxin is produced by some strains of C. difficile (binary toxin is also known as C. difficile transferase (CDT).
The role of Binary toxin in C. difficile infection is uncertain: Some studies suggest that Binary toxin increases bacterial adherence to host cells and promotes cell death; others report that the toxin suppresses eosinophil activity. It is possible that the toxin has multiple virulence effects.
Infection: Gastrointestinal
C. difficile infection acts on the colon, where it induces a range of gastrointestinal issues, from mild diarrhea to severe colitis.
Pseudomembranous colitis is the most serious form of C. difficile infection; characterized by yellowish-white exudate on the mucosal surface of the colon. The pseudomembrane comprises fibrin and inflammatory cells in mucus.
Treatment & Prevention:
Withdrawal of the associated antibiotic often suffices to treat diarrheal symptoms.
Metronidazole or vancomycin can be administered in more serious cases.
Colitis relapse is common. Patients with multiple relapses may benefit from fecal microbiota transfer from a healthy donor, which replenishes the healthy bacteria in the colon.
Clostridium perfringens
Spores are rarely seen clinically, and, that colonies are flat and irregular; it is beta-hemolytic.
C. perfringens can be divided into subtypes based on toxin production.
Virulence factors:
Alpha toxins cause hemolysis, vascular leakage, liver toxicity, and cardiac dysfunction. Present in all C. perfringens subtypes.
Several other toxins form pores and/or induce necrosis.
Food poisoning enterotoxins alter the intestinal membrane permeability, leading to fluid and ion loss; like some other bacterial toxins, this enterotoxin is a superantigen.
Infection: Soft Tissue & Food Poisoning
Soft tissue infections, including cellulitis, fasciitis, myositis, and myonecrosis.
Myonecrosis, aka, gas gangrene, which is a life-threatening disease that destroys muscle tissues. Bacterial metabolic activity produces characteristic gas bubbles, which appear as purlplish-black bulges under the skin. Tissue necrosis and other complications can lead to death.
Food poisoning typically results from consumption of contaminated meat products; the enterotoxin acts on the small intestine to produce abdominal cramps and watery diarrhea without fever or vomiting.
Treatment & Prevention:
Soft tissue infections:
Treatment for C. perfringens soft-tissue infections includes antibiotics and surgical debridement of necrotic tissues.
Proper wound care is essential for prevention of infection.
Food poisoning:
Treatment for food poisoning includes rehydration; antibiotics are not recommended because this type of food poisoning is self-limiting.
Prevention is achieved by refrigerating and thorough reheating of foods to at least 74 degrees Celsius.
Clostridium tetani
Distinctive tennis-racket shape during spore formation.
Extremely oxygen sensitive, and spores can survive for extended periods of time in the soil.
Infection typically occurs when wounds encounter contaminated soil.
Wounds provide ideal necrotic and anaerobic environments for C. tetani growth.
Virulence factors:
Tetanospasmin is a heat-labile neurotoxin that blocks the release of inhibitory neurotransmitters, such as GABA and glycine.
The neurotoxin is endocytosed, then transported along axons to reach neuronal somas in the spinal cord.
Because it blocks inhibitory neurotransmitter release, neuronal excitatory activity is unregulated.
Tetanolysin is another toxin produced by C. tetani.
It is an oxygen-labile hemolysin thought to promote tissue necrosis.
Infection: Tetanus
Spastic paralysis is the characteristic feature of tetanus.
– This can manifest systemically or locally as lockjaw, grimace (aka, risus sardonicus), and opisthotonos, in which spasms of the extensors of the head, neck, and back produce extreme back extension. Tetanus can also cause fever and sweating.
Cephalic tetanus involves the cranial nerves.
Maternal tetanus is associated with pregnancy, specifically, contamination during medical or spontaneous abortion and delivery.
Neonatal tetanus occurs when infection spreads from the umbilical stump.
Treatment & Prevention:
Vaccination effectively prevents tetanus.
Treatment for infection involves wound debridement and administration of metronidazole and antitoxins are necessary to prevent death.
Clostridium botulinum
Foodborne disease: the spores tend to contaminate vegetables and meat.
Toxins are protected from degradation within the gastrointestinal tract.
Virulence factors:
Exotoxins A-G.
Types A, B, and E are responsible for most human infections.
Toxins are pre-formed, particularly in canned goods, which provide ideal alkaline and anaerobic environments.
From the gut, the neurotoxins are absorbed and delivered to motor neurons; upon endocytosis, neurotoxins block acetylcholine release at peripheral motor junctions.
Infection: Botulism
Descending flaccid paralysis, blurred vision with dilated pupils, dry mouth, and constipation.
Respiratory failure leads to death.
Wound infection produces similar symptoms; in the US, this form is associated with injection drug use.
Treatment & Prevention:
Treatment includes metronidazole or penicillin and antitoxins.
Respiratory support may be necessary, and gastric irrigation can aid in toxin removal.
Prevention of botulism involves boiling of home-canned goods and discarding damaged cans.
Honey can contain C. botulinum organisms, so it should not be given to infants because they have not yet acquired the competitive microflora that prevents C. botulinum survival in adults.
References
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. Medical microbiology. Philadelphia: Elsevier/Saunders. (2013).
Levinson, W. E. Review of Medical Microbiology and Immunology. 14th Ed. Lange (2016).
Cowardin, C.A., Buonomo, E.L., Saleh, M.M., Wilson, M.G., Burgess, S.L., Kuehne, S.A., et al. (2017). Nat Microbiol. 1(8):16108. doi:10.1038/nmicrobiol.2016.108.
Eckert, C., Emirian, A., Le Monnier, A.L., Cathala, L., De Montclos, H., Gorget, J., et al. (2015). New Microbe and New Infect. 3:12-17.
Images
Pseudomembranous colitis (Wikipedia; Author Ed Uthman).
Gas gangrene (Wikipedia; Authors Engelbert Schröpfer, Stephan Rauthe and Thomas Meyer).
C. tetani (Centers for Disease Control Public Health Image Library).