This document provides an overview of various food intoxications, covering bacteria such as Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, and toxins including ciguatera, scombroid, tetrodotoxin, and domoic acid from contaminated shellfish. It describes the organisms and toxins involved, foods commonly associated with poisoning, symptoms, mechanisms of toxicity, and treatments for each type of food intoxication.

1. An overview of food
intoxications
Andrew Bayat, PGY-2
3/30/2015, 3/31/2015

3. Topics
 Staphylococcus aureus
 Bacillus cereus
 Clostridium perfringens
 Clostridium botulinum
 Ciguatera
 Scombroid
 Tetrodotoxin
 Amnesic shellfish poisoning
 Other shellfish poisonings
 Safe foods?

4. Other topics to consider
 Clostridium difficile
 EIEC, EHEC, STEC, Shigella
 ETEC
 Salmonella
 Vibrio cholera and parahaemolyticus
 Camypylobacter jejuni
 Bacillus anthracis
 Yersinia enterocolitica
 Mushroom intoxications
 Heavy Metal ingestions
 Radioactive ingestions
 Tyramine, MSG, Metabisulfate, preservatives, flavoring
 Common Plant toxins: hemlock, nightshade, wisteria, fox-
glove, hydrangea, oleander, etc
 Solvents, paints, industrial exposures, pesticides

5. Staphylococcus aureus
 One of the most common causes of food
poisoning and the most common toxin-mediated
form of food poisoning
 Bacteria is colonized on the food source, can
replicate at 10-40 °C.
 Forms one of several heat stable (120 °C)
Exotoxins, prior to ingestion.
◦ Believed to be >10 toxins, commonest being
Exotoxin B
 Common food sources are milk, cream, meats,
egg, mushrooms.

6. Staphylococcus aureus
 Onset of symptoms is rapid: 1-6 hours
 Resolution is rapid: ~24 hours
 Treatment is supportive care
 Mechanism for producing symptoms is
unclear
◦ Thought to be increased intestinal serotonin
release, possibly increased vagal tone, and/or
direct irritation/inflammation to the mucosa
 Symptoms:

7. Bacillus cereus
 Gm + rod, motile, non encapsulated, spore-
forming
 Spores can survive up to 100 °C
 Commonly on foods that have been
improperly cooked below 100 °C, thus
endospores survive.
 #1 vector is fried rice, then non-fried rice,
then meat

8. Bacillus cereus
 Two forms of illness are caused by B.
cereus
 Treatment for both is supportive
◦ 1. Diarrheal form: 6-24 hours incubation then
nausea, abdominal cramps and watery
diarrhea.
 Due to germination of endospores in the small
intestine making heat labile toxin, tripartite hemolysin B
similar to heat labile toxin of ETEC.
◦ 2. Emetic form: similar to Staph enterotoxin in
character: 1-6 hour incubation then nausea,
vomiting and abdominal pain/cramps
 Due to germination of spores during ambient
temperatures (classically a buffet), these then make
heat-stable (and acid-stable) toxin, cereulide.
 Syndrome Usually lasts <10 hours.

9. Toxin cellular targets
5-HT3 Receptor
Beta-Barrel

10. Clostridium perfringens
 Anaerobic Gm + spore forming rod. Several
strains exist.
◦ Forms heat resistant spores that when deposited
on food, survive normal cooking/heating temperature
(100 °C)
◦ Spores germinate during preparation between 12°C
- 60°C
◦ Proliferates very rapidly between 30°C -50°C
◦ Symptoms start 6-24 hours after ingestion
◦ Once ingested, forms several toxins in the intestine
◦ No defined food vehicle but usually meat, poultry,
gravy
◦ Also responsible for gas gangrene

11. Clostridium perfringens
 Strain A:
 Most common strain causing enteral disease
in Industrialized countries.
◦ Toxin, which may be encoded via plasmid or
chromosomal.
◦ Creates 46kDa “CPE” enterotoxin.
 Binds extracellular Claudin 3 and Claudin 4 on
extracellular domain.
 Causes: 1) Cellular pore formation and 2) disassembly of
tight junctions and thus the paracellular pathway.
 Heat labile at 74 °C
◦ Leads to cell death and increased
cellular/membrane permeability
 Treat with IVF, no antibiotics recommended
for enteral infection

12. CPE mechanism
Calpain
Apoptosi
s

13. CPE mechanism
Tight Junction

14. Clostridium perfringens
 Strain B and C
 Forms 34 kDa Beta-toxin, which is similar to
Staphylococcal alpha toxin.
◦ Heat labile, normally digested by trypsin-> disease
predisposed by malnutrition
◦ Beta strands, heptamerize into a Beta-barrel which
causes a pore in the cell membrane
◦ Result is K efflux, Ca influx, cellular swelling and cell
death
 May infect small bowel namely jejunum
(occasionally ileum) and result in Clostridial
necrotizing enteritis, AKA: Pigbel, Darmbrand.
◦ Characterized by bloody diarrhea, small bowel
ulceration, perforation, peritonitis.
 Usually treat with abx: Metronidazole, Pen G

15. Clostridium botulinum
 Anaerobic gm + spore forming rod.
Motile.
◦ 4 (I-IV) major groups with groups I and II
causing human disease.
◦ In adult disease, toxins are pre-formed by the
bacteria then released upon bacterial death.
 Formed in anaerobic environment with suitably low
acidity and salinity
 Toxin is heat labile and destroyed at 85 °C
◦ Usually in association with eating canned
foods that are not properly heated/prepared.

16. Clostridium botulinum
 There are at least 7 types of neurotoxin, all
somewhat similar in size, structure and function
150kDa.
◦ Absorbed through the intestinal M cell, utilizing
hemagglutinin
◦ Heavy chain one portion of the molecule is
responsible for binding a nerve cell another portion is
responsible for inserting the light chain into the nerve
cell.
◦ The light chain is a Zinc peptidase that cleaves
SNAP, and VAMP
◦ SNAP and VAMP are molecules that are responsible
for exocytosis of neurotransmitter containing vesicles
at the neuromuscular junction.
◦ Result is that neurotransmitter (Ach) is not released
into the synapse

17. Clostridium botulinum toxin

18. Clostridium botulinum
 Symptoms delayed 12-72 hours: Symptoms
include: nausea and vomiting evolving into
descending paralysis involving cranial
nerves: dysphagia, dysphonia, dysarthria,
facial weakness/droop (usually bilateral), and
respiratory failure.
 Death rate is 5-10%
 Treatment is supportive care and Heptameric
despeciated (no Fc portion) equine IgG to the toxin

19. Scombroid poisoning
 Most common cause of fish-related
food poisoning in the US.
 Associated with improperly prepared
Scombridae family of fish: mackerel,
tuna, blue-fish, tuna, bonito.
 Sometimes caused by non-
scombroids: mahi-mahi, amberjack

20. Scombroid poisoning
 Presents 30-60 minutes after ingestion
with flushing, diaphoresis, abdominal
pain/cramping, nausea, vomiting,
diarrhea headache, urticaria,
tachycardia, bronchospasm/wheezing,
and angioedema.
◦ Essentially resembles allergic reaction
◦ Lasts 10-24 hours if untreated
◦ Treatment is usually histamine blockade
◦ Severe cases can require IM epinephrine,
steroids, ventilator support

21. Scombroid poisoning
 Cause is Histidine in the muscle content of
the fish:
◦ Histidine is converted to Histamine by E. coli,
Klebsiella pneumoniae, Morganella morganii
using Histidine decarboxylase.
◦ Occurs at temperatures >18 °C; thus
predominates in fish that is improperly frozen
◦ Because Histamine is heat stable, once formed
smoking, cooking or canning the meat will not
eliminate the toxin
Histadine decarboxylase

22. Ciguatera
 Name of the common cause of food
intoxication caused by eating predatory
reef fish including Red Snapper, Grouper,
Jack, Barracuda, etc contaminated with
Ciguatoxin.
◦ Toxin is formed by Diflagellate sp (namely
Gambierdiscus toxicus) which are eaten along
with algae by herbivorous fish and biomagnify
up the food chain
◦ Concentrates in head, roe, and viscera

23. Ciguatoxin
 Onset of symptoms 1-30 hours, usually
within 12h; may last months to years.
◦ Symptoms usually start with GI: nausea,
vomiting, weakness.
◦ Progress to neurological: paresthesia,
dysuria, blurred vision, hot-cold sensation
reversal, loose/painful teeth, cold
allodynia, and rarely dyspareunia
◦ May occasionally have bradycardia,
hypotension.
 Several toxins may be present but the
predominant toxin is Ciguatoxin
◦ Heat stable, acid stable, tasteless and
odorless
◦ Not modified by handling or cooking process

24. Ciguatoxin
 Mechanism is lowering the potential for voltage-
gated sodium channels in the CNS,
predisposing neurons to depolarization.
◦ Toxin is lipid soluble and able to cross the BBB
◦ No completely effective treatment; no validated
treatments
◦ Calcium channel blockers including nifedipine,
TCAs, mannitol have been used with variable
success
◦ Lethal in concentrations of 0.45 ug/kg

25. Tetrodotoxin
 Pre-formed toxin present in puffer-fish, trigger-fish,
porcupine-fish, blue-ringed octopus among others.
◦ Formed by commensal bacteria, usually Vibrio sp.
◦ Toxin usually concentrated in liver, ovaries, eyes, with
much lower concentrations if at all in the flesh and skin of
fish.
◦ Fugu is the Japanese dish of puffer-fish, prepared but a
specially trained chef- usually requiring 2-3 years of
specialized training. Available in ~17 restaurants in the
US.
◦ Poisoning happens in the setting of inappropriately
prepared foods.
◦ Toxin is heat-stable and potentiated by some cooking
temperatures, thus soups are frequently associated with
worse cases of toxicity

26. Tetrodotoxin
 Symptoms start within 30 minutes of
ingestion
◦ Lip/Tongue paresthesia, abdominal pain,
nausea, vomiting, weakness, tremor, ataxia,
dysphagia, dysphonia, ascending paralysis,
bronchospasm, hypotension, bradycardia
and respiratory failure/ arrest
◦ LD50 is roughly 300 ug/kg= 25-30mg would
kill 50% average adults
◦ Death occurs at ~4-6 hours, most those who
survive 24 hours go on to survive.
◦ No antidote available, although there is
research on a monoclonal Ab.

27. Tetrodotoxin
 Mechanism is inhibition of voltage-
gated sodium channels, inhibiting
depolarization in nerve and muscle
cells.

28. Amnesic Shellfish Poisoning
 Caused by eating filter-feeding shellfish
contaminated by the toxin, domoic acid.
◦ Shellfish include bivalve mollusks: mussels,
clams, oysters, scallops. Also can be found in
anchovies.
◦ Toxin is formed by diatomaceous
phytoplankton (type of algae) and biomagnify
in shellfish
◦ First seen 1987 in Prince Edward Island,
Canada
◦ Toxin is heat stable and not inactivated by
routine cooking

29. Amnesic Shellfish poisoning
 Symptoms can start 15 minutes-38
hours after ingestion (usually delayed
by 24h)
◦ Symptoms usually begin with GI: Nausea,
vomiting, diarrhea, abdominal pain
◦ Then develop Headache, dizziness,
weakness, seizure, altered mental status.
◦ 10% develop antegrade memory loss
◦ Treatment is supportive care, no known
antidote

30. Amnesic Shellfish poisoning
 Domoic acid
◦ Structurally similar to glutamate
◦ Causes toxicity by binding and exciting
AMPA/KA subset of Glutamate receptors
in the neurons and astrocytes of the CNS,
especially the Amygdala and
Hippocampus.
 Binding of the receptor causes increased
intracellular calcium, activation of caspases
and ultimately apoptosis

31. Neurotoxic Shellfish poisoning
 Also in Bivalves
 Caused by eating shellfish
contaminated by toxin formed by
dinoflagellate and associated
temporally with red-tides.
◦ Toxin is coined “brevetoxin” and is
structurally and functionally similar to
Ciguatoxin (increased excitability) with
similar symptoms

32. Paralytic Shellfish poisoning
 Also in Bivalves
 Caused by toxin, Saxitoxin made by
dinoflagellates, again associated with red-
tides.
◦ Inhibits neuronal voltage-gated sodium channels
in a similar fashion to tetrodotoxin, causing
inhibition of neuronal action potential
◦ Similar symptoms to tetrodotoxin: nausea,
vomiting followed by tingling lips, weakness,
ataxia and ascending paralysis
◦ Deadly in doses estimated ~5 ng/kg

33. Voltage gated sodium
receptor

34. In summary, what is safe to
eat?

35. Well maybe not completely
safe…

36. Amazon reviews…

37. Thanks
 Chief residents
 Dr. Kleinschmidt
 Dr. Cutrell

38. References
 Agata N, Ohta M, Mori M, Isobe M (1995). "A novel dodecadepsipeptide, cereulide, is an emetic toxin
ofBacillus cereus". FEMS Microbiol Lett 129 (1): 17–20. doi:10.1016/0378-1097(95)00119-
P.PMID 7781985.
 Lee CH, Ruben PC (2008). "Interaction between voltage-gated sodium channels and the neurotoxin,
tetrodotoxin". Channels (Austin)2 (6): 407–12. doi:10.4161/chan.2.6.7429. PMID 19098433
 Lelong, A.; Hégaret, H.; Soudant, P.; Bates, S. S. (2012). "Pseudo-nitzschia (Bacillariophyceae)
Species, Domoic Acid and Amnesic Shellfish Poisoning: Revisiting Previous
Paradigms".Phycologia 51 (2): 168–216. doi:10.2216/11-37.1
 Caya JG, Agni R, Miller JE (June 2004). “Clostridium botulinum and the clinical laboratorian: a detailed
review of botulis, including biological warfare ramifications of the botulinum toxin.” Arch. Pathol. Lab.
Med. 128 (6): 653–62. doi10.1043/1543-2165(2004)128<653:CBATCL>2.0.CO;2. PMID 15163234
 CDC - Botulism, General Information - NCZVED". Cdc.gov. Retrieved 2014-02-12.
 Mitchell, Leslie A., and Michael Koval. "Specificity of interaction between Clostridium perfringens
enterotoxin and claudin-family tight junction proteins."Toxins 2.7 (2010): 1595-1611.
 Lindström, Miia, et al. "Novel insights into the epidemiology of Clostridium perfringens type A food
poisoning." Food microbiology 28.2 (2011): 192-198.
 Robertson, Susan L., and Bruce A. McClane. "Interactions between Clostridium perfringens
enterotoxin and claudins." Claudins. Humana Press, 2011. 63-75.
 Popoff, Michel R. "Clostridial pore-forming toxins: Powerful virulence factors."Anaerobe 30 (2014):
220-238.
 Matsumura, T., Sugawara, Y., Yutani, M., Amatsu, S., Yagita, H., Kohda, T., ... & Fujinaga, Y. (2015).
Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity. Nature
communications, 6.
 Carter, A. T., & Peck, M. W. (2014). Genomes, neurotoxins and biology of Clostridium botulinum Group
I and Group II. Research in microbiology.

39. References
 Tsutsuura, S., & Murata, M. (2012). [Temperature dependence of staphylococcal enterotoxin A
production by Staphylococcus aureus]. Nihon rinsho. Japanese journal of clinical medicine, 70(8),
1323-1328.
 Hu, D. L., & Nakane, A. (2014). Mechanisms of staphylococcal enterotoxin-induced
emesis. European journal of pharmacology, 722, 95-107.
 Beecher, D. J., Schoeni, J. L., & Wong, A. C. (1995). Enterotoxic activity of hemolysin BL from
Bacillus cereus. Infection and Immunity, 63(11), 4423-4428.
 Schoeni, J. L., & Lee Wong, A. C. (2005). Bacillus cereus food poisoning and its toxins. Journal of
Food Protection®, 68(3), 636-648.
 Agata, N., Ohta, M., Mori, M., & Isobe, M. (1995). A novel dodecadepsipeptide, cereulide, is an
emetic toxin of Bacillus cereus. FEMS microbiology letters,129(1), 17-19.
 Tortorella, V., Masciari, P., Pezzi, M., Mola, A., Tiburzi, S. P., Zinzi, M. C., ... & Verre, M. (2014).
Histamine Poisoning from Ingestion of Fish or Scombroid Syndrome. Case reports in emergency
medicine, 2014.
 Hungerford, J. M. (2010). Scombroid poisoning: a review. Toxicon, 56(2), 231-243.
 Lehane, L., & Lewis, R. J. (2000). Ciguatera: recent advances but the risk remains. International
journal of food microbiology, 61(2), 91-125.
 Palafox, N. A., & Buenconsejo-Lum, L. E. (2001). Ciguatera fish poisoning: review of clinical
manifestations. Toxin Reviews, 20(2), 141-160.
 Bane, V., Lehane, M., Dikshit, M., O'Riordan, A., & Furey, A. (2014). Tetrodotoxin: Chemistry,
toxicity, source, distribution and detection. Toxins,6(2), 693-755.
 Giordano, G., Kavanagh, T. J., Faustman, E. M., White, C. C., & Costa, L. G. (2013). Low-level
domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: role of
glutathione. toxicological sciences, kft002.
 Todd, E. C. (1993). Domoic acid and amnesic shellfish poisoning-a review.Journal of Food
Protection®, 56(1), 69-83.
 Pulido, O. M. (2008). Domoic acid toxicologic pathology: a review. Marine Drugs, 6(2), 180-219.