The central market in
Bangalore, India.
Food safety standards
barely exist in most of
the developing world.
A street vendor goes with his instinct to know when
his kabobs are ready to eat in Bangalore, India.
Mushrooms come from Canada,
peppers from the Netherlands,
squash from California.
A global harvest supplies
Seattle’s Pike Place Market.
Raw products are responsible
for an increasing percentage
of foodborne diseases.
To combat Salmonella,
Arkansas graduate student
sprays “healthfull” bacteria
onto chicks to determine
if they can out-compete
harmfull bacteria
in their intestinal tracts.
Production
Processing
Distribution
Preparation
ENTEROBACTERIACEAE

Escherichia coli

SALMONELLA

SHIGELLA

YERSINIA

Yersinia pestis (urban plaque, sylvatic
plaque)

Yersinia enterocolitica
ENTEROBACTERIACEAE
(cont.)

Klebsiella pneumoniae

Proteus mirabilis

Enterobacter, Citrobacter, Serratia, Providencia

Helicobacter pylori
Escherichia coli
Septicemia
Urinary Tract Infections
Neonatal Meningitis
Gastroenteritis
SALMONELLA
Enterocolitis
Septicemia
Enteric Fever
Asymptomatic (chronic)
carriage
SHIGELLA
Dysentery









YERSINIA

Yersinia pestis (urban plaque, sylvatic plaque)

Yersinia enterocolitica
Klebsiella pneumoniae
Proteus mirabilis
Enterobacter, Citrobacter, Serratia, Providencia
Helicobacter pylori
Enterobacteria




The largest, most heterogeneous collection of
pathogenic Gram-negative bacilli.
Normal flora of the GIT of humans and animals.
Present worldwide in soil, water and vegetation excretion from the GIT.
Responsible for 30-35% of all septicemias, over 70% of
urinary tract infections, and many intestinal infections.
Shigella, Salmonella and Yersinia pestis

Always associated with disease.

NOT found as normal flora in the human.
E. coli, Klebsiella pneumoniae and Proteus mirabilis

Commensals that can cause opportunistic infections.
Enterobacteria infections
can originate from:

Animal reservoir (most Salmonella infections)

Human carrier (Shigella and Salmonella typhi)

Endogenous spread (Escherichia coli)
Enterobacteria
Physiology and Structure





Gram-negative bacilli, motile or non-motile,
do not form spores.
Aerobes and facultative anaerobes.
Simple nutritional requirements, ferment
glucose, reduce nitrate.
Catalase-positive and oxidase-negative.
Some members of the family have prominent
capsules (e.g., Klebsiella).
Enterobacteria
Serological Classification



The O antigen - the outer polysacharide portion
of lipopolysaccharides (LPS)
The K antigen - capsular polysaccharide (Vi in
Salmonella typhi)
The H antigen - on the flagellar proteins
Enterobacteria
Virulence Factors

Endotoxin (LPS)

Capsule


Antigenic Phase Variation - to evade antibody
response - alternative expression of capsular
[K] and flagellar [H] antigens
Exotoxin production
Enterobacteria
Virulence Factors
(cont.)

Expression of Adhesion Factors (fimbriae)

Intracellular Survival and Multiplication
(invasion, replication and spread in the colonic epithelium)

Sequestration of Growth Factors/Iron
(siderophores and hemolysins)

Resistance to Serum Killing

Antimicrobial Resistance
A shadow-cast
electron micrograph
of E. coli showing
flagella.
Scanning electron
micrograph showing
E. coli interacting
with human mast cell
E. coli - Clinical Syndromes

Septicemia

Urinary Tract Infections

Neonatal Meningitis

Gastroenteritis (five groups)
E. coli - Clinical Syndromes


(cont.)
Septicemia - originates from infections in the
urinary tract or the GIT.
Neonatal meningitis -
E. coli and group B streptococci (S. agalacatiae) the most common cause of neonatal meningitis.
E. coli - Clinical Syndromes

(cont.)
Urinary Tract Infections - over 80% of communityacquired urinary tract infections and the majority of
hospital-acquired infections (urinary catheters).
Ascending infections - originate from the GIT, attach to
urethra epithelium, ascend into the bladder, and may
migrate to the kidney or prostate.
These strains produce adhesins, which bind to cells
lining the bladder and upper urinary tract.
E. coli
Gastroenteritis - five groups:
1. Enterotoxigenic E. coli (ETEC) - "travelers' diarrhea"
2. Enteroinvasive E. coli (EIEC)
3. Enteropathogenic E. coli (EPEC)
4. Enterohemorrhagic E. coli (EHEC) -
E. coli strain O157:H7
5. Enteroaggregative E. coli (EAggEC)
E. coli
1. Enterotoxigenic E. coli (ETEC) - enterotoxins stimulate
secretion and fluid loss. Secretory diarrhea follows 1-2 day
incubation period and persists for 3-4 days (mild
symptoms, cramps, nausea, vomiting, watery diarrhea;
"travelers' diarrhea".
2. Enteroinvasive E. coli (EIEC) - invade and destroy the
colonic epithelium.
3. Enteropathogenic E. coli (EPEC) - enteroadherent
E. coli (pediatric diarrhea in impoverished countries).
Drug Therapies Used to Treat Moderate to Severe
Traveler's Diarrhea in Adults
Ciprofloxacin (Cipro), 500 mg twice daily for one to three days,
or one 750-mg dose (if diarrhea resolves)
Norfloxacin (Noroxin), 400 mg twice daily for one to three days
Ofloxacin (Floxin), 300 mg twice daily for one to three days
Trimethoprim-sulfamethoxazole (Bactrim DS),
160 mg/800 mg twice daily for three days
Doxycycline (Vibramycin), 100 mg twice a day for three days
-----------------------------------------------------------------------NOTE: In the absence of dysentery, loperamide (Imodium A-D), two 2-mg tablets
at the start of diarrhea, followed by one 2-mg tablet after each loose stool
(maximum daily dosage: 8 mg), can be used with any of the antibiotic therapies.
The Taj Mahal
E. coli
4. Enterohemorrhagic E. coli (EHEC) - produces verotoxin.
The most common strains producing disease in developed countries.


The CDC estimates 20,000 cases/year in the U.S.;
200 people die; 2-7% of infected individuals develop
hemolytic uremic syndrome (HUS), and of those 3-5% die,
with 33% left with lingering kidney problems.
Symptomes: from mild diarrhea to hemorrhagic colitis
with severe abdominal pain, bloody diarrhea (dysyntery),
no fever; HUS (acute renal failure, thrombocytopenia,
hemolytic anemia).
E. coli
4. Enterohemorrhagic E. coli (EHEC) - produces
verotoxin.
E. coli O157:H7 is NOT a problem if food is
thoroughly cooked, BUT ~62,000 (Science, May,
2001) or ~73,000 (National Geographic, May, 2002)
people are infected each year in the U.S.,
and 60 – most of them children - die.
E. coli O157:H7 can survive the gentle heating of
rare hamburgers.
Enterohemorrhagic E. coli (EHEC)
Outbreaks of infection by E. coli strain O157:H7:



The first cases - 1982 and 1983 - undercooked hamburgers.
1991 - cider pressed from apples that had fallen into
manure and were not washed.
1999 - the cow manure-water chain outbreaks of infection
at the county fairs.
5. Enteroaggregative E. coli (EAggEC) - persistent watery
diarrhea with vomiting and dehydration in
infants in developing countries.
SALMONELLA




Salmonella are found in virtually all animals
(poultry, livestock, rodents, domestic animals,
birds) and humans.
Salmonella typhi (capsule) and Salmonella
paratyphi are highly adapted to man and do
NOT cause disease in non-human hosts.
Other Salmonella strains are adapted to animals
and when they infect humans, can cause severe
human disease (Salmonella choleraesuis).
Many strains cause disease in both humans and
animals.
SALMONELLA
The source of most infection:



Contaminated water or food products (poultry,
eggs, dairy products)
Direct fecal-oral spread in children (pet turtles in
the U.S.)
Salmonella typhi - ingestion of food and water
contaminated by infected food handlers
(foreign travel) (no animal reservoir).
SALMONELLA - Clinical Syndromes


Enterocolitis - the most common form of
salmonellosis, symptoms 6 to 48 hours after
consumption of the contaminated food or water
(nausea, vomiting, non-bloody diarrhea, fever,
abdominal cramps, myalgia, headache).
Septicemia
SALMONELLA - Clinical Syndromes


Enteric Fever - Typhoid Fever (S. typhi)
Paratyphoid Fever - (S. paratyphi A)
Incubation period 10-14 days; increasing remittent
fever (headache, myalgias, malaise, anorexia)
then gastrointestinal symptoms.
This cycle corresponds to an initial bacteremic
phase followed by reinfection of the intestines.
SALMONELLA
Asymptomatic (chronic) carriage - after typhoid and
paratyphoid fever, 1-5% patients,
gall bladder - reservoir.
Typhoid vaccine - Two typhoid vaccines are currently
available for use in the U. S.:
1. An oral, live, attenuated vaccine (Vivotif Berna
vaccine, manufactured from the Ty21a strain of S. typhi
by the Swiss Serum and Vaccine Institute).
2. A Vi capsular polysaccharide vaccine (ViCPS) (Typhim
Vi, manufactured by Aventis Pasteur) for intramuscular
use.
Both vaccines - protect 50%–80% of recipients.
SHIGELLA

Four species (non-capsulated):
S. dysenteriae, S. flexneri, S. boydii, S. sonnei.

Shigellosis (bacterial dysentery) is primarily
a pediatric disease.


Endemic disease in adults (contact with infected
children).
Epidemic outbreaks - day-care centers, nurseries,
etc.
SHIGELLA




Shigellosis - the fecal-oral route, contaminated
hands ("disease of dirty hands"),
less commonly in water or food.
In contrast to Salmonella infections, food-borne
disease is uncommon.
The only reservoir is the human intestine.
Epidemic outbreaks - between soldiers during
wars, in concentration camps; contemporary
wars - refugee camps.
SHIGELLA -
Pathogenesis and Immunity

Shigella remain localized in the ileum and colon.

Produce exotoxins - cytotoxic, enterotoxic and
neurotoxic (cell death and necrosis).

Invade the intestinal epithelium - the intense
inflammatory response characterized by
bloody, mucopurulent diarrhea (dysentery).
SHIGELLA - Clinical Syndromes




Abdominal cramps, diarrhea, fever and bloody
stools.
Symptoms - 1 to 3 days after the bacilli are
ingested.
Colonize the small intestine and begin to
multiply within the first 12 hours.
The initial sign - profuse water diarrhea is
mediated by an enterotoxin.
SHIGELLA - Clinical Syndromes



Abdominal cramps and tenesmus, pus and
blood in the stool (invasion of the colonic
mucosa, destruction of superficial mucosal
layer and production of mucosal ulceration).
Bacteremia is uncommon.
Infection is usually self-limited - antibiotic
treatment is recommended to reduce the risk of
secondary spread (family members).
YERSINIA

Yersinia pestis

Y. pseudotuberculosis

Y. enterocolitica

All Yersinia infections are zoonotic, with
human as the accidental hosts.
Yersinia pestis




XIV century, epidemic plaque [the "Black Death"] claimed 25 million people.
Urban plaque - spread between rats or from rats
to humans by infected fleas.
With effective control of rats and better hygiene,
urban plaque has been eliminated from most
communities.
Sylvatic plaque - persists today in many
countries, including the U.S. (prairie dogs, mice,
rabbits, rats and flea vectors are widespread).
Yersinia enterocolitica

Enterocolitis - diarrhea, fever, abdominal pain
(children, pseudoappendicitis).

Transmission from animal sources is usually by
contaminated food or water.
Klebsiella pneumoniae

Isolated from the oropharynx and the GIT of
~5% of healthy people.

Community acquired primary lobar pneumonia.

Wound and soft tissue infections.

Urinary tract infections (nosocomial).

Otitis and sinusitis.

Large capsule protects against phagocytosis.
Proteus mirabilis

Common infection of the urinary tract.

Highly mobile, producing urease.

Urease - hydrolysis of urea into CO2 and NH3,
this raises the urine pH and facilitates the
formation of kidney stones.
Enterobacter, Citrobacter,
Serratia, Providencia

Associated with hospital-acquired
infections in patients with a compromised
immune system.
Helicobacter pylori





Gram-negative pathogen colonizes the human
stomach (1982).
Infection is acquired during childhood, persists
lifelong if not eradicated (50% of the world's
human population is chronically infected).
Chronic gastritis, and an increased risk of
peptic ulcer disease and gastric cancer.
Highly motile (flagella; corkscrew motility).
A neutral pH-optimum urease enables gastric
colonization.
Condoriri Region (Bolivia 2005)