Enterics

Enterobacteriaceae are facultative anaerobes, sugar fermenters, and oxidase negative. Differentiating them requires lactose media.

Subgroups can be identified through serotyping: O-antigen, H-antigen, K-antigen, and Vi-antigen.

Escherichia coli (E. coli)

Normal bacteria which plays a role in digestion and Vitamin K2 production. It is the most abundant facultative anaerobe.

Only pathovars (E. coli variants) are disease causing and have evolved horizontal gene transfer amongst other tools to maintain virulence. Examples include uropathogenic (UTIs) and diarrheagenic E. coli.

Enterotoxigenic E. coli (ETEC)

The most common pathovar. It is transmitted through fecal contamination.

It expresses one or both of either Heat Labile toxin (LT), which is nearly identical to the cholera toxin, and Heat Stable toxin (ST), which mimics the intestinal hormone guanylin and leads to elevated cAMP in secretory cells and downstream chloride release into the lumen.

Enterohemorrhagic E. coli (EHEC)

Causes hemorrhagic colitis and bloody diarrhea. Tends to grow around livestock and spreads though contamination of food or water. Only a low dose is required for infection.

This organism produces disease through a pathogenicity island which alters epithelial cells, creating attaching and effacing lesions. It also produces the Shiga toxin, targeting the Gb3 receptor on endothelial cells, which makes it a Shiga Toxin E. coli (STEC).

Many patients go on to experience hemolytic uremic syndrome (HUS) which results in anemia, thrombocytopenia, and renal failure.

Clinical pearl: Diagnosing and treating a Shiga Toxin E. coli

Stool should be cultured for 0157, or tested for Shiga toxin protein/O-antigen directly.

Antibiotic use is NOT recommended as it signals to the prophage to start replicating and increases the toxin production. Instead, supportive therapy is recommended and the infection will usually resolve in 5-8 days.

Salmonella

It is lactose negative and produces H2S. It has the highest incidence in children younger than five and in the elderly.

There are six major subspecies of Salmonella enterica (I - VI). However, S. Bongori has also be isolated in humans. It is transmitted through foods (eggs, poultry, flour, milk, ect.). However, a high dose is necessary for infection.

Another genus is Salmonella Shigella, which is nonmotile and lactose negative. This is another pathovar of E. coli. It causes bacillary dysentery, resulting in urgency, tenesmus, and bloody stools.

Pathogenesis

Salmonella pathogenicity island 1 (SPI1) encodes a type III secretion system which invades cells rather than produces toxins. The secreted molecules change the morphology of epithelial cells and induces IL-8, IL-1beta, and IL-18 which leads to inflammation.

There is a human specific serotype of Salmonella (S. Typhi and S. Paratyphi) which will cause Typhoid fever. Because these subtypes invade macrophages, the infection is systemic and bacteria will generally spread first to the liver and then to the gallbladder. Some patients will be chronic carriers.

Salmonella dysenterie type 1

This is the only Salmonella Shigella which produces the Shiga toxin.

It also transgresses the epithelium by being invasive. It is taken up by M cells into Peyer's patches, using a type III secretion system to phagocytose bacteria. It is non-motile, so it uses the actin system to move around.

It induces apoptosis in gut epithelium, creating a massive inflammatory response, resulting in bloody stool and fecal leukocytes.

Yersinia

Lactose negative, psychrophilic (likes cold climates), bipolar staining. Found around domestic animals (especially pigs).

Good prevention with the Typbar-TCV vaccine, which is long lasting.

Significant species

Y. enterocolitica (most common)
Y. pseudotuberculosis
Y. pestis (associated w/ plague)

Campylobacter

Gram negative, microaerophilic (likes low atmospheres), thermophilic (likes hot climates), non-sugar fermenter, oxidase positive, encapsulated. Found around domestic animals (most animals are carriers). The largest carrier is poultry.

Seen as bloody diarrhea as the bacteria transgresses into the epithelial layer, producing a strong inflammatory response.

Sialic acid containing lipopolysaccharides on C. jejuni membrane mimics the nervous system. This induces cross-reactive antibodies against GM1, GM2, and GD1a and creates peripheral neuropathy. Can result in Guillain-Barre Syndrome, as molecular mimicry results in an autoimmune response which targets myelin.

Diagnosis

Examination of fecal bacteria, looking for a curved/helical rod shape. Specialized media can also be used, as well as rapid antigen tests on fecal specimens.

Significant species

C. jejuni (most common)
C. coli
C. upsaliensis
C. fetus (causes septicemia rather than GI infection)

Vibrio

Gram negative, curved rod shape, oxidase positive, facultative anaerobe, halophilic (likes high salt concentration - V. cholerae is the exception to this)

V. cholerae

Found in marine and estuarine environments. Contaminates water and food. Disease is associated with O1 and O139 serogroups. Diagnosed through darkfield microscopy, TCBS agar, or immunoassay. (for O serotypes).

The vibriophage binds to TCP pili of V. cholerae and encodes for the cholera toxin. It does not invade the mucosa, instead attaching to the intestinal wall and secreting the toxin. The cholera toxin binds to GM1-ganglioside receptors, activating the Gs pathway and increasing cAMP, altering CFTR and resulting in profuse, watery diarrhea.

Oral vaccines

Dukoral: Whole cell (O1 + recombinant B subunit)
Shanchol/mORCVAX/Euvichol: Whole cell (O1, O139)
Vaxchora: Live, attenuated (O1)

V. parahaemolyticus

Found near the coast in raw/undercooked seafood.

Haemolysins are lipids and proteins responsible for lysis of RBCs. It has thermostable haemolysin (Tdh), Tdh-related haemolysin (Trh).

V. vulnificus

Found in marine environments.

Open wound in seawater can result in a rapid necrotic wound infection (fulminant septicemia).

Future Concerns

Constant evolution of pathogens can result in new clinical presentations. For example, the Shiga-Toxin producing E. coli outbreak in 2011 came from a recent combination of virulence profiles between Shiga-Toxin producing E. coli and enteroaggregative E. coli.

Higher temperatures from climate change are associated with higher incidence of Campylobacter, E. coli, Salmonella, and Vibro. Incidence fluctuates due to temperature changes throughout the year.