populate the concept map with terms from the lecture PowerPoint and draw/label any connections between terms.
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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
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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
• 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
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
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
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
