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 ...