1/30/22 1 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 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 1/30/22 2 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 •  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 1/30/22 3 TIIISS injects proteins into mammalian cells that are NOT normally phagocytic to 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 1/30/22 4 Holden, Traffic, 2002 Invading macrophages Paul (Ed.), Fundamental Immunology, 2003 Holden, Traffic, 2002 Salmonella Containing Vacuoles 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) 1/30/22 5 PhoQ is activated by molecular signals inside ...

1. 1/30/22
1
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
1/30/22
2
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
1/30/22
3
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
1/30/22
4
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)

6. 1/30/22
5
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