Clostridium perfringens- Pathogenesis, Clinical Features

Clostridium perfringens- Pathogenesis, Clinical Features

Clostridium perfringens- Pathogenesis, Clinical Features

  • Clostridium perfringens (previously named Clostridium welchii) is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium, which is found commonly in decaying vegetation and soils. 
  • Along with many environmental sources, it is also found in the intestines of humans and animals. 
  • Clostridium perfringens is the causative agent of a number of human diseases, such as gas gangrene and food poisoning, and many diseases of animals.

Clostridium perfringens- Pathogenesis, Clinical Features

Image Source: Centers for Disease Control and Prevention (CDC) and https://doi.org/10.1186/s13567-017-0413-x.

Virulence Factors

  • Clostridium perfringens, which produces a huge array of invasins and exotoxins, causes wound and surgical infections that lead to gas gangrene, in addition to severe uterine infections.
  • The virulence of  C. perfringens is attributable largely to its ability to produce at least 16 different toxins and extracellular enzymes. However, no single strain produces this entire toxin panoply. 
  • Clostridium perfringens produces many different toxins, four of which (alpha, beta, epsilon, iota) can cause potentially deadly syndromes. The toxins cause damage to tissues, blood cells, and blood vessels.
  • Clostridial hemolysins and extracellular enzymes such as proteases, lipases, collagenase, and hyaluronidase, contribute to the invasive process. 
  • Clostridium perfringens also produces an enterotoxin and is an important cause of food poisoning.
  • The CPE (for Clostridium perfringens enterotoxin) is a polypeptide of 35.5 kDa that accumulates at the beginning of the sporulation and is excreted to the media when it lysates at the end of the sporulation. It is coded by the CPE gene, present in less than the 5% of the type A strains, and it can be located in the chromosome or in an external plasmid.

Pathogenesis

Invasive infection and Gas gangrenes

  • In invasive clostridial infections, spores reach tissue either by contamination of traumatized areas (soil, feces) or from the intestinal tract.
  • The spores germinate at low oxidation-reduction potential; vegetative cells multiply, ferment carbohydrates present in the tissue, and produce gas.
  • The distention of tissue and interference with blood supply, together with the secretion of necrotizing toxin and hyaluronidase, favor the spread of infection.
  • Tissue necrosis extends, providing an opportunity for increased bacterial growth; hemolytic anemia; and, ultimately, severe toxemia and death.
  • The toxin involved in gas gangrene is known as α-toxin, which inserts into the plasma membrane of cells, producing gaps in the membrane that disrupt normal cellular function.

Diarrheal disease ( C. perfringens type A food poisoning)

  • Illness is caused by eating food contaminated with large numbers of  C. perfringens bacteria that produce enough toxin in the intestines to cause illness.
  • C. perfringens can survive high temperatures. During cooling and holding of food at temperatures from 54°F–140°F (12°C–60°C), the bacteria grows. It can grow very rapidly between 109°F–117°F (43°C–47°C).
  • If the food is served without reheating to kill the bacteria, live bacteria may be eaten. The bacteria produce a toxin (CPE toxin for Clostridium perfringens toxin) inside the intestine that causes illness.
  • Upon ingestion of heavily contaminated food, vegetative cells of a chromosomal CPE strain survive passage into the intestines, where they initially multiply but then soon sporulate; Spo0A and alternate sigma factors control both in vivo sporulation and CPE production.
  • The toxin accumulates in the mother cell until it is released at the completion of sporulation when the mother cell lyses.
  • The released toxin then acts, to damage the intestines and trigger diarrhea and abdominal cramping.

Clinical Features

Gas gangrene

  • Clostridium perfringens is the most common strain of clostridia associated with trauma-induced gas gangrene in humans and is also a major cause of spontaneous (nontraumatic) gas gangrene.
  • The classic features of gas gangrene are extensive local tissue destruction progressing to profound shock and death.
  • From a contaminated wound (eg, a compound fracture, postpartum uterus), the infection spreads in 1–3 days to produce crepitation in the subcutaneous tissue and muscle, foul-smelling discharge, rapidly progressing necrosis, fever, hemolysis, toxemia, shock, and death.
  • At times, the infection results only in anaerobic fasciitis or cellulitis.

Food Poisoning

  • perfringens food poisoning usually follows the ingestion of large numbers of clostridia that have grown in warmed meat dishes.
  • The toxin forms when the organisms sporulate in the gut, with the onset of diarrhea and abdominal cramps—usually without vomiting or fever—in 7–30 hours.
  • The illness suddenly begins and lasts only 1–2 days.

References

  1. Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2013). Medical microbiology. Philadelphia: Elsevier/Saunders.
  2. https://www.cdc.gov/foodsafety/diseases/clostridium-perfringens.html
  3. https://www.sciencedirect.com/topics/medicine-and-dentistry/clostridium-perfringens
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372840/
  5. https://www.jstor.org/stable/4481235?seq=1#page_scan_tab_contents
  6. https://www.researchgate.net/publication/13910870_Pathogenesis_of_Clostridium_perfringens_Infection_Mechanisms_and_Mediators_of_Shock
  7. https://mmbr.asm.org/content/55/4/649
  8. https://watermark.silverchair.com
  9. http://textbookofbacteriology.net/clostridia_2.html
  10. https://mmbr.asm.org/content/77/2/208

Clostridium perfringens- Pathogenesis, Clinical Features

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