Chapter 122. Acute Infectious Diarrheal Diseases and Bacterial Food Poisoning (Part 2)

Pathogenic MechanismsEnteric pathogens have developed a variety of tactics to overcome host defenses. Understanding the virulence factors employed by these organisms is important in the diagnosis and treatment of clinical disease.Inoculum SizeThe number of microorganisms that must be ingested to cause disease varies considerably from species to species. For Shigella, enterohemorrhagic Escherichia coli, Giardia lamblia, or Entamoeba, as few as 10–100 bacteria or cysts can produce infection, while 105–108Vibrio cholerae organisms must be ingested orally to cause disease. The infective dose of Salmonella varies widely, depending on the species, host, and food vehicle. ...
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Chapter 122. Acute Infectious Diarrheal Diseases and Bacterial Food Poisoning (Part 2) Chapter 122. Acute Infectious Diarrheal Diseases and Bacterial Food Poisoning (Part 2) Pathogenic Mechanisms Enteric pathogens have developed a variety of tactics to overcome hostdefenses. Understanding the virulence factors employed by these organisms isimportant in the diagnosis and treatment of clinical disease. Inoculum Size The number of microorganisms that must be ingested to cause diseasevaries considerably from species to species. For Shigella, enterohemorrhagicEscherichia coli, Giardia lamblia, or Entamoeba, as few as 10–100 bacteria orcysts can produce infection, while 105–108Vibrio cholerae organisms must beingested orally to cause disease. The infective dose of Salmonella varies widely,depending on the species, host, and food vehicle. The ability of organisms toovercome host defenses has important implications for transmission; Shigella,enterohemorrhagic E. coli, Entamoeba, and Giardia can spread by person-to-person contact, whereas under some circumstances Salmonella may have to growin food for several hours before reaching an effective infectious dose. Adherence Many organisms must adhere to the gastrointestinal mucosa as an initialstep in the pathogenic process; thus, organisms that can compete with the normalbowel flora and colonize the mucosa have an important advantage in causingdisease. Specific cell-surface proteins involved in attachment of bacteria tointestinal cells are important virulence determinants. V. cholerae, for example,adheres to the brush border of small-intestinal enterocytes via specific surfaceadhesins, including the toxin-coregulated pilus and other accessory colonizationfactors. Enterotoxigenic E. coli, which causes watery diarrhea, produces anadherence protein called colonization factor antigen that is necessary forcolonization of the upper small intestine by the organism prior to the production ofenterotoxin. Enteropathogenic E. coli, an agent of diarrhea in young children, andenterohemorrhagic E. coli, which causes hemorrhagic colitis and the hemolytic-uremic syndrome, produce virulence determinants that allow these organisms toattach to and efface the brush border of the intestinal epithelium. Toxin Production The production of one or more exotoxins is important in the pathogenesisof numerous enteric organisms. Such toxins include enterotoxins, which causewatery diarrhea by acting directly on secretory mechanisms in the intestinalmucosa; cytotoxins, which cause destruction of mucosal cells and associatedinflammatory diarrhea; and neurotoxins, which act directly on the central orperipheral nervous system. The prototypical enterotoxin is cholera toxin, a heterodimeric proteincomposed of one A and five B subunits. The A subunit contains the enzymaticactivity of the toxin, while the B subunit pentamer binds holotoxin to theenterocyte surface receptor, the ganglioside GM1. After the binding of holotoxin, afragment of the A subunit is translocated across the eukaryotic cell membrane intothe cytoplasm, where it catalyzes the ADP-ribosylation of a GTP-binding proteinand causes persistent activation of adenylate cyclase. The end result is an increaseof cyclic AMP in the intestinal mucosa, which increases Cl – secretion anddecreases Na+ absorption, leading to loss of fluid and the production of diarrhea. Enterotoxigenic strains of E. coli may produce a protein called heat-labileenterotoxin (LT) that is similar to cholera toxin and causes secretory diarrhea bythe same mechanism. Alternatively, enterotoxigenic strains of E. coli may produceheat-stable enterotoxin (ST), one form of which causes diarrhea by activation ofguanylate cyclase and elevation of intracellular cyclic GMP. Some enterotoxigenicstrains of E. coli produce both LT and ST. Bacterial cytotoxins, in contrast, destroy intestinal mucosal cells andproduce the syndrome of dysentery, with bloody stools containing inflammatorycells. Enteric pathogens that produce such cytotoxins include Shigella dysenteriaetype 1, Vibrio parahaemolyticus, and Clostridium difficile. S. dysenteriae type 1and Shiga toxin–producing strains of E. coli produce potent cytotoxins and havebeen associated with outbreaks of hemorrhagic colitis and hemolytic-uremicsyndrome. Neurotoxins are usually produced by bacteria outside the host and thereforecause symptoms soon after ingestion. Included are the staphylococcal and Bacilluscereus toxins, which act on the central nervous system to produce vomiting. Invasion Dysentery may result not only from the production of cytotoxins but alsofrom bacterial invasion and destruction of intest ...