This document discusses Salmonella Typhi and Salmonella Typhimurium, the bacteria that cause typhoid fever and gastroenteritis respectively. It notes that S. Typhi only infects humans, causing an estimated 21 million cases and 200,000 deaths worldwide each year. S. Typhimurium has a broader host range and is a leading cause of foodborne illness in the US, causing an estimated 6.5 million cases annually. The document outlines the pathogenesis of typhoid fever and gastroenteritis, noting that S. Typhi spreads through contaminated food/water while S. Typhimurium is often associated with poultry/eggs. It also discusses the Salmonella virulence factors that allow

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BIOL 315: Salmonella and
Typhoid fever
Dr. Sean Murray
Western Blot
Typhoid Fever
Typhoid Fever
• Salmonella Typhi: only infects humans
• CDC estimates 21 million cases per year world wide
with 200,000 deaths
• 400 cases per year in USA (most traveled to developing
countries)
Gastroenteritis
• Salmonella Typhimurium: broad host range
• CDC estimates 6.5 million cases a year in USA
with ~9,000 deaths from gastroenteritis
• 1/3 of all gastroenteritis infections caused by
Salmonella
• CDC: 15 Salmonella infections per 100,000

2. people in USA
Typhoid Fever
• Salmonella Typhi
• Fecally contaminated food/water
• 1-4 weeks post-ingestion for symptoms
• Multiply in spleen, liver
• High fever, chills, convulsions, delirium, and
anorexia for 2-3 weeks
• Pass from liver to gall bladder to intestine,
where it may ulcerate the intestinal mucosa
(fatal)
• Treatment: antibiotics
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Typhoid Mary, early 1900s
• Salmonella can persist in the gall
bladder, and may be shed in feces
• Chef Typhoid Mary was a carrier
• She infected many people as she
worked at hotels, restaurants, hospitals

3. • Arrested twice, spent the rest of her life
in prison after the second arrest
Gastroenteritis
• Salmonella Typhimurium
• Contaminated poultry/eggs
– Caesar salad, raw eggs
• Nausea, vomiting 6-24 hours post ingestion
• Followed by abdominal pain, diarrhea, fever
• Symptoms last 1 week
• Shed Salmonella in feces for up to 3 months
• 1-3% of people shed for 1 year
• If enters bloodstream, septic shock (rare)
• Antibiotics not normally prescribed
Species infected by Salmonella
• Humans (Typhi)
• Humans, mice, cows, most mammals,
C. elegans (Typhimurium)
Salmonella Invasion of intestinal epithelium
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TIIISS injects proteins into mammalian
cells that are NOT normally phagocytic to

4. induce phagocytosis of bacterium
Galan and Wolf-Watz, Nature, 2006
Type III-secretion system (TIIISS)
Galan and Wolf-Watz, Nature, 2006
Secretion protein complex is sequentially assembled
starting with the inner membrane, outer membrane,
periplasm, and finally the extracellular domains
Galan and Wolf-Watz, Nature, 2006
Invasion of intestinal epithelium
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Holden, Traffic, 2002
Invading
macrophages
Paul (Ed.), Fundamental Immunology, 2003
Holden, Traffic, 2002
Salmonella
Containing
Vacuoles

5. Holden, Traffic, 2002
Salmonella Pathogenicity Islands SPI-1 and SPI-2
encode two different TIIISS that were horizontally
acquired (different GC content than chromosome);
pSLT is self-transmissible
pSLT
Spi-1
Spi-2
Salmonella
chromosome
Genome = chromosome plus plasmid
How does Salmonella adapt to
being inside or outside host cells?
In bacterial
membrane:
In bacterial
cytoplasm:
PhoQ
PhoP
(sensor)
(transcription factor)

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PhoQ is activated by molecular signals inside host cell
PhoP becomes activated inside macrophages: Activated
PhoP represses the transcription of SPI-1 TIIISS prg
genes(PhoP-repressed genes); shuts off SPI-1 TIIISS so
SPI-2 TIIISS can protect Salmonella containing vacuoles
Galan and Wolf-Watz, Nature, 2006
Salmonella virulence factors
• PhoQ/PhoP, SPI-1 TIIISS, SPI-2 TIIISS
• Salmonella also contains a virulence
plasmid called pSLT
• SPI-1 TIIISS is needed for invasion but
not persistence
• SPI-2 TIIISS, pSLT, and PhoP/Q are
required for persistence (most important
factors for causing disease)
Summary virulence factors
• SPI-1 TIIISS is needed for oral invasion,
but is not needed if Salmonella injected
directly into the bloodstream
• SPI-2 TIIISS, PhoP/Q, and pSLT are

7. needed for survival within host cells
– They protect Salmonella containing
vacuoles
SPI-1 TIIISS
Induces membrane
ruffling, entry
SPI-2 TIIISS,
PhoQ/PhoP,
pSLT proteins
Protect
Salmonella-
Containing
Vacuoles
Adadpted from Paul (Ed.), Fundamental Immunology, 2003