Bacterial Toxins Mechanism Quiz

E. coli

• Similar molecules seen in other organisms as well
• LT (Heat-Labile Toxin) ADP-ribosylates a G protein, causing permanent activation of adenyl cyclase and resulting in efflux of water from the cell
• ST (Heat-Stable Toxin) has an overall effect similar to LT but works via cGMP
• Hemolysins, such as a-hemolysin, similar to those of staph and strep, are channel formers
• Contact secretion system: a molecular "syringe" possessed by certain E. coli, allowing for the injection of macromolecules into cells and causing major cytoskeletal rearrangement
• Intimin: an important adhesin found in certain E. coli serogroups

Pathogenic E. coli Strains

• Classified into four groups based on serology and pathogenic behavior:
  • Enterotoxigenic E. coli (ETEC)
  • Enteropathogenic E. coli (EPEC)
  • Enterohemorrhagic E. coli (EHEC)
  • Enteroinvasive E. coli (EIEC)

Enterotoxigenic E. coli (ETEC)

• Causes traveler's diarrhea or Montezuma's revenge
• Important cause of infant diarrhea in developing countries
• Acts on cyclic nucleotides
• Pathogenesis dependent on LT and ST toxins and CFA (colony formation antigen)-type pili
• Non-invasive, damage readily reversible

Enteropathogenic E. coli (EPEC)

• A major cause of diarrheal illness in small children
• No toxins in the classic sense, but damaging substances involved
• Contact secretion system injects cytoskeletal inhibiting agents, leading to decrease in surface area and absorption
• Disrupts cytoskeletons of microvilli on intestinal lining cells, causing attachment and effacement (A/E) lesions
• Malabsorptive diarrhea, reversible

Enterohemorrhagic E. coli (EHEC)

• Mainly O157:H7
• Reservoir in cattle
• Shiga toxin plus A/E lesions
• Very low infectious dose (100-200 cells)
• Causes bloody diarrhea leading to dysentery and HUS (Hemolytic Uremic Syndrome) in about 10% of cases
• HUS: glomerulus contains many receptors for toxin, leading to renal failure and death

Salmonella

• Similar in many respects to E. coli
• About 2000 named serotypes, formerly considered species, now all classified as "S. enterica"
• Two principal disease manifestations: enteritis (so-called "Salmonella food poisoning") and enteric fever (historic name "typhoid fever")
• People most likely to have a bad outcome: small children (immune system has yet to develop) and elderly people (due to poor stomach acid)
• Requires an actual organism infection, better referred to as food-borne infection
• Can be transmitted through contaminated foodstuffs, dairy products, eggs, poultry, and plant material

Salmonella Enteritis

• Mechanism of pathogenesis unclear, but contracted chiefly from contaminated foodstuffs
• Symptoms (nausea, vomiting, maybe fever, etc.) may be due to inflammation or enterotoxin activity
• Considerable spectrum of severity

Salmonella Enteric (Typhoid) Fever

• Totally human, due to S. enterica serotype Typhi
• Can grow in bile, highly bile resistant, and readily survives macrophages
• Systemic infection with a weeks-long time course, can be very damaging
• Important to understand the survival and growth of the organism in macrophages

Borrelia

• Large, microaerophilic, and will grow on artificial media
• Many are carried by arthropods (most often ticks or lice)
• Two most important conditions: relapsing fever and Lyme disease
• Relapsing fever: due to B. hermsii, carried by body lice, fever comes and goes over months
• Lyme disease: caused by B. bergdorferi, found in land with vegetation, and carried by Ixodes ticks (eastern and western deer ticks)
• First stage: rash (bull's eye, erythema migrans)
• Second stage: cardiac and/or nervous symptoms, usually resolve in weeks
• M. pneumoniae responsible for about 10% of pneumonia ("walking" pneumonia)

Ureaplasma urealyticum

• Identified with urethritis (males) and possibly a variety of other conditions, exact role/significance unclear
• Commonly seen resident flora organism in the GU tract

Spirochetes (Order Spirochetales)

• Gram negative organisms with unusual spiral morphology and unique means of motility (endoflagella within periplasmic space)
• Motility sometimes called "spinning and flexing"
• Bending in the middle
• Commonly seen in many animals, including humans, especially in the oral cavity
• Can be difficult to visualize under light microscope, hard to see and stain due to very thin structure

Treponema pallidum and Syphilis

• Strictly human, difficult to grow except in tissue culture at low oxygen concentration
• Abscess-like structure that is triggered by type 4 hypersensitivity
• Syphilis is a classic granulomatous disease in many respects
• Three stages: primary, secondary, and tertiary, with latent phase between secondary and tertiary