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The 50% infectious dose (ID₅₀) corresponds to the minimum number of organisms required to cause disease in 50% of exposed individuals.  When controlling for the route of exposure and overall health of the host, the ID₅₀ is generally correlated inversely with degree of disease communicability.

The organism in Line 2 (Salmonella) has an ID₅₀ of approximately 10⁷, whereas the organism in Line 1 has a much lower ID₅₀ of about 10².  Of the given options, the organism with the lowest ID₅₀ is Shigella flexneri.  Depending on the species, as few as 10 Shigella organisms can cause disease.

The low ID₅₀ of Shigella is related to virulence factors expressed in various locations in the gastrointestinal tract:

• Stomach:  Shigella can survive a low-pH environment, the primary reason for its low ID₅₀.  On exposure to acidic conditions, Shigella species upregulate the transcription of pH-resistant virulence genes, making them relatively resistant to degradation in the stomach.  This characteristic is in contrast to the acid-sensitivity of Salmonella, which contributes to its higher ID₅₀.

• Proximal small intestine:  Bile salts are normally bactericidal, but exposure to them upregulates production of adhesin proteins and promotes formation of Shigella biofilms.

• Distal small intestine:  Shigella invades cells forming the epithelial barrier and can spread to other cells laterally (ie, cell-to-cell spread) without reentering the gut lumen.

Other organisms that can cause diarrhea with a small inoculum include Campylobacter jejuni (500 organisms), Entamoeba histolytica (1-10), and Giardia lamblia (1-10).

(Choices A and D)  Like Salmonella, Clostridium perfringens and Vibrio cholerae are acid sensitive and thrive in more alkaline conditions, requiring a relatively high ID₅₀ (10⁴-10⁸).

(Choice B)  Some strains of Escherichia coli that cause gastroenteritis (eg, Shiga toxin–producing E coli) have a low ID₅₀ due to their ability to survive an acidic environment, similar to Shigella.  However, enterotoxigenic E coli is less adaptive to extreme acidity and therefore has a higher ID₅₀.

(Choice E)  Yersinia pestis, which causes the plague (eg, fever, buboes), has an extremely low ID₅₀ (<10 organisms) when transmitted via the subcutaneous route (eg, fleas). In contrast, Yersinia enterocolitica (fecal-oral transmission, diarrheal illness) has a higher ID₅₀; although this bacterium produces urease, making it somewhat acid resistant, its growth is improved in more alkaline conditions.

Educational objective:
Shigella species require a low infectious dose to cause gastrointestinal disease.  The mechanism primarily involves their ability to survive in the acidic (low pH) gastric environment.