Food & Water Borne Pathogens

Food & Water Borne Pathogens

• Classified as infections or intoxications

• Determining etiology depends on

  • Incubation period

  • Symptoms

  • Duration

  • Demographics

Food Poisoning from Intoxication

• Clostridium botulinum

  • Anaerobic, endospore forming

  • Endospores form in intestines of animals & can pass in feces

  • Reach soil / plants in manure and organic fertilizers

• Source: home canning, botox use

  • Spores are killed only at temperatures > 100°C

  • Endospores will germinate in anaerobic environment and release botulism toxin. Bacteria often die, but toxin remains in food

Botulism Toxin

• A-B type binary toxin

• Human lethal dose -<1 μg

• Route: intestine to blood to peripheral nerves

• A peptidase destroying the protein components of exocytosis apparatus, preventing release of acetyl choline (release of excitatory impulses) resulting in flaccid paralysis

Botulism (Illness)

• Initial symptoms: blurred vision, slurred speech, difficulty swallowing, etc

  • Begins hours to days after ingestion depending on dose

• Flaccid paralysis continues to move downward to limbs & trunk

• Death occurs due to paralysis of muscles controlling the respiratory tract

• Treatment: antibodies to prevent binding of toxin to cells

  • Recovery can take days to weeks with treatment; there is the possibility that patients will not fully recover

Infant Botulism (Infection)

• Ingestion of endospores (eating honey) followed by germination of endospores in the neutral stomach of the infant and production of toxin by bacterial cells

  • Q: How might the treatment for this be different?

  • A: Since it is a bacterial infection it can be treated with antibiotics

Staphylococcal Food Poisoning

• Source: foods containing poultry, egg & dairy products

• Original source: food preparation

  • Nose, genitals, boil / abscesses

• Staph can grow over a wide range of temperatures (8-45°C) and pH

  • Slight chilling will not prevent growth

• Intoxification: bacteria are usually destroyed but enterotoxin remains

  • Toxins are odorless, tasteless, heat stable, acid stable

  • Toxins are phage encoded

    • SEA, SEB, SEC, SED, SEE, SEF, SEG, SEH, SEI

    • 30-50% of strains may contain one or more

  • Toxins are superantigens; overstimulating normal gut immune response resulting in more severe response

• Short incubation of 1-6 hours; often abrupt / severe onset

  • Mostly vomiting with no fever, some diarrhea

GI Infections

Vibrio cholerae

• Comma shaped G-

• Polar flagella (motile)

• Millions of cases and tens to hundreds of thousands of deaths annually

Cholera

• Habitat

  • Naturally found in low concentrations in fresh / salt water

  • Can become concentrated in shellfish - reference as ‘unclean animals’ so watch for undercooked seafood!

  • Associated with copepods; transport by ocean currents, el nino events

  • Also becomes concentrated in human intestines; fecal contamination of water has had major impact

• Vibrio is sensitive to acid so how does it cause GI illness?

  • Very high numbers may be needed

  • Malnutrition helps to reduce stomach acid

  • People taking antacids are more susceptible

• Cholera strains are differentiated by O antigens (LPS)

  • We’ve had 7 pandemics since 1800s, most beginning around Indian ocean

• Cholera toxin: causes uncontrolled activation of adenylate cyclase; leading to increased cAMP; increased output of ions followed by secretion of water

  • “Ricewater” stool

  • Lose up to 15 liters of water per day

  • Severe hydration may lead to hypovolemic shock

• Treatment

  • Antibiotics may speed recovery but disease is self limiting

  • More important to replace fluids

    • Fluids must be coupled with glucose - triggers uptake of sodium (followed by water) by glucose / Na+ transporter

Campylobacter

• Most common cause of gastroenteritis in US & other developed countries

• Curly G- bacillus

• Polar flagellum (motile)

• Oxidase neg / nonfermenting

• Grow at 42°C

• Microaerophilic

Campylobacter jejuni

• Corkscrew motillity helps invade intestinal lining

• Cytolethal distending toxin: binary type toxin that causes double stranded breaks in DNA causing arrest of cell cycle / mitosis and eventually cell death

  • Symptoms are not specific or diagnostic of infection

  • 2-7 day incubation

  • Recovery in less than a week so antibiotics rarely necessary

• Association with Guillain-Barre syndrome — autoimmune disease of peripheral nervous system leading to temporary paralysis of limbs

  • Cross-reactivity of campylobacter surface antigens and nerve cell antigens

Helicobacter pylori

• Curved (motile)

• G- bacillus

• Polar flagella

Link — H. pylori & Gastric Ulcers

• Isolated from ulcer biopsies, however 50% of adults are colonized by age 50; nearly all are colonized in developing countres

• Initially no animal models to satisfy Koch’s postulates

  • Required human volunteer (Barry Marshall)

• Combination antibiotic treatment and proton pump inhibitors eliminate ulcers and prevents recurrences

H. pylori Virulence Factors

• Regulated by Hsb

• Urease (urea → CO2 & NH3) & acid inhibitory protein combat stomach acid

• Mucinase and phospholipase help to invade mucous lining (gastric mucus protects from acid)

• Corkscrew motility with flagella help penetrate mucous lining

• Vacuolating cytotoxin - key difference between low virulence and highly virulent

Is H. pylori Beneficial or Harmful?

• The presence of H. pylori might be linked to adult t2 diabetes

• People with Parkinson’s Disease are more likely to be infected with H. pylori

• People without H. pylori are at greater risk for acid reflux and esophageal cancer

• People without H. pylori are more prone to allergy-induced asthma

  • Remember that the vacuolating cytotoxin is not present in all strains

Salmonella typhi

• Found in human intestinal tract (can cross into blood stream)

• Transmission is fecal to oral (sewage system breakdown, food prep)

Salmonella typhimurim

• Less severe

  • Only attaches and invades intestinal cells; cannot cross into blood stream

  • Live in animal intestines (poultry, eggs)

Salmonella

• Have high resistance to environmental conditions allowing them to survive (not grow) outside human body

  • 5 F’s: fingers, flies, food, fluid, fields

• Have colonized plants and infected plant cells

• Type III secretion system

  • On contact with the epithelial cell, salmonellae assemble the type III secretion system (T3SS) and translocate effectors into the eukaryotic cytoplasm

  • Results in the rearrangement of the actin cytoskeleton into membrane ruffles

  • Lost of surface area for absorption, leading to diarrhea

  • Induction of signaling cascade turns on the inflammatory response. In addition destabilization of tight junctions allows leakage and access of bacteria to the basolateral surface

    • Salmonella can survive in macrophage to be transported around body

Typhoid Fever - Salmonella typhi

• Long incubation time of 5-21 days as bacteria cross intestinal cells into blood stream

• Gradually rising fever ending with high fever and rose spots

• Patients are often lethargic and delirious

• Bacteria re-enter intestinal tract through gall bladder

• Ulceration of intestine during this second round may cause distention, bloody stools, & sharp abdominal pain

Shigella

• Found in human intestine (can carry asymptomatically)

• Transmission: fecal / oral

  • Food prep, breakdown in sewage systems

  • Has a very low infectious dose (100 cells) due to high acid tolerance

• Invades the epithelial cells of the small intestine

• Only S. dysenteriae possess the Shiga toxin

  • A-binary type toxin with 5-B chanis

  • Targets translation process leading to cell death of intestinal cells

  • Results in bloody diarrhea

Pathogenic E. coli Strains

• ETEC

• EPEC

• EHEC

• EIEC

• EaagC

  • All have acquired virulence genes from other intestinal pathogens

  • Horizontal gene transfer

Enterotoxigenic E. coli (ETEC)

• Heat-labile toxin

  • LT-1: identical to cholera toxin but much less potent

• ETEC also produces another enterotoxin known as the heat-stable toxin (STa) which mimics Guanylin

Enteropathogenic E. coli (EPEC)

• Attachment and effacement

  • Use of Type III secretion system to inject attachment receptor (Tir) into intestinal cell

  • Bacterial intimin binds Tir protein within intestinal cell membrane

  • Disruption of cell signaling disrupts actin arrangement

• Loss of villi causes decrease in absorption

Enterohemorhagic E. coli (EHEC)

• Attachment & effacement just like EPEC strains

• What sets EHEC apart from EPEC?

  • Stx-1, Shiga-like toxin

  • Acquired from Shigella via transduction

• Hemolytic uremic syndrome may result from Shigella-like toxin (stx-2) binding to kidney cells

  • Decreased urine output, followed by blood in urine, ending in kidney failure

Enteroinvasive E.coli (EIEC)

• Acquired invasion genes from Shigella

• No Shiga toxin

Listeria monocytogenes

• Found in animal intestinal tracts, soil, plants

• Psychrotrophic

• Usually acquired by consuming contaminated hot dogs, deli meats and cheeses

Listerosis

• In immunocompetent individuals

  • Influenza or gastroenteritis-like illness

• In immunosuppressed patients

  • Systemic infection, meningitis

• In neonatal infants via transplacental transmission

  • Meningitis

How It Works

• Internalization

• Lysis of vacuole by pore-forming toxin Listeriolysin O

• Polymerization of actin tails permit movement

• Projection into neighboring cells

• Lysis of double membrane by listeriolysin and phospholipase

C. difficile

• C. difficile pseudomembranous enterocolitis often after prolonged antibiotic treatment

  • Clostridium difficile is a normal part of the microbiome but levels are kept low by normal flora

  • Toxin A & B are responsible for pus filled diarrhea and necrosis of mucosa (interfere with internal cell signaling)

  • Severe cases can result in grossly dilated colon which could rupture