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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

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