The Key Events Dose-Response Framework: Its Potential for Application to Foodborne Pathogenic Microorganisms

Figures & data

Figure 1 Key biological events occurring between intake of pathogen and the specific effect of concern (fetal listeriosis). At each event, both host and pathogen factors can be examined with regard to: i) how they may influence probability of progression toward the effect of concern (i.e., how they affect the number of organisms exiting a given event, given the number of organisms entering the event), and ii) how they influence inter- and intra- host response variability.

Table A-1 Overview of Mechanistic Catagories for Pathogenic Bacteria

Toxigenic bacteria: Produce preformed toxins in foods

Staphylococcus aureus produces a highly heat stable enterotoxin. This bacterium is traditionally associated with products that have been temperature abused sufficiently to allow S. aureus to attain high levels and produce its enterotoxins. Even if food is subsequently cooked, the extreme heat stability of the enterotoxin would result in illness.

Clostridium botulinum neurotoxin (BoTN) is produced during the growth of C. botulinum – an obligate anaerobe and spore former – in canned foods, various fermented, dried or salted meat and fish that are not properly produced and/or refrigerated, and various other foods where the oxygen content is limited. The toxin appears to be associated with the outer bacterial cell coat and is sloughed off into the food product as the culture grows.

Toxicoinfectious bacteria: Colonize surface of the GI tract

One subgroup (e.g., Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC)) delivers toxin directly into epithelial cells to which the bacterium has attached. Once inside the epithelial cell, the enterotoxins typically affect cyclic AMP- or cyclic GMP-mediated net Cl^− secretion, often resulting in severe diarrhea.

A second subgroup (e.g., enterohemorrhagic E. coli [EHEC]), colonize the surface of endothelial cells and elicit toxin (Shiga toxin (Stx)), which locally disrupts the integrity of the intestinal tract, most likely as a means of acquiring limiting nutrients such as iron. Focal necrosis of epithelial cells leads to the primary adverse effect - hemorrhagic colitis (HC). Stx is also taken up by the host and transported to distant internal tissue where it can lead to primary sequelae - hemolytic uremic syndrome (HUS).

A third subgroup (e.g., Clostridium perfringens) produces an enterotoxin associated with sporulation. Microorganism typically sporulates poorly in foods so high levels of enterotoxin are not observed. When microorganisms are ingested, cells sporulate in the intestinal tract, undergo autolysis, and enterotoxin is released into the lumen.

Invasive bacteria: Invade across intestinal epithelium and disseminate within the host

One subgroup (e.g., Salmonella enterica, Shigella spp. and enteroinvasive E. coli) invades the epithelium, spreads intercellularly, and causes focal microulcerations of the mucosa.

A second subgroup (e.g., Yersinia enterocolitica and Yersinia pseudotuberculosis) crosses the epithelium and proceeds to regional lymph nodes, causing severe abdominal pain and, occasionally, mesenteric lymphadenitis. Campylobacter jejuni may also translocate across the mucosa and survive submucosally, but does not typically reach the bloodstream.

A third subgroup (e.g., Salmonella Typhi and Paratyphi, Listeria monocytogenes) translocates across the epithelium, and may then be transported to distal sites in the host (e.g., spleen, liver, and bone marrow, brain).