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Frontal vs Stealth Attack Strategy. Characteristics? Symptoms Timespan Immune involvement. Frontal Attack Strategy I. Vibrio cholerae – cholera epidemics First reportable disease in the United States. Spread by fecal contaminated food/water.
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Frontal vs Stealth Attack Strategy • Characteristics? • Symptoms • Timespan • Immune involvement
Frontal Attack Strategy I • Vibrio cholerae – cholera epidemics • First reportable disease in the United States. • Spread by fecal contaminated food/water. • Rapid secretory diarrhea caused by cholera toxin (CT). • Horizontal transfer of genetic material by CT phage leads to virulence, non-01 Vibrios can also cause disease. • Seventh pandemic began in Indonesia in 1900’s, V. cholerae 01 El Tor, now endemic in Asia and Africa.
FIG. 1. Schematic representation of the genetic regulatory cascade controlling CT expression. From top to bottom the diagram shows activation of tcpP by AphAB, basal repression of toxT by H-NS, activation of toxT by TcpP-TcpH and ToxR-ToxS with displacement of H-NS, activation of tcpA and ctxA by ToxT, and synthesis of TcpA and CT. Different patterns indicate the various regulators. RNAP, RNA polymerase. Small arrows beneath boxes indicate promoters, as well as the direction of transcription. A wavy thick line indicates mRNA and thus indicates transcriptional activation. Vibrio cholera toxin (CT) regulation: Sanchez et al., 2004. Expression of Cholera Toxin under Non-AKI Conditions in Vibrio cholerae El Tor Induced by Increasing the Exposed Surface of Cultures. J. Bacteriology 186: 1355-1361.
Rivera et al., 2001. Genotypes associated with virulence in environmental isolates of Vibrio cholerae. AEM 67: 2421-2429.
Frontal Attack Strategy II • Yersinia pestis – Plague • 1894, French scientist Yersin discovered the bacteria. Normally found in rodents, transmitted by fleas. • Bacterium binds to macrophages, uses Type III secretory system to inject toxic molecules (YOPs = Yersinia Outer Proteins) into cell. Macrophages die in great numbers. • Bubonic plague named for large, painful swellings ("buboes") in lymph nodes of neck, groin, or armpit. 3 days later, high fever, delirious, black splotches due to hemorrhaging under skin. Often buboes would burst, agonizing frenzy for victims. • 1346-1352: "The Great Pestilence", killed one out four people in Europe, N. Africa & Middle East. 70-80% of those who got it died within 5 days. http://www.sp.uconn.edu/~terry/229sp03/lectures/microbial_diseases.html http://plagueyersiniapestis.homestead.com/YERSINIAPESTIS.HTML
Yersinia pestis • Fleas that ingest bacteria get bacterial growth in gut, blocks food flow. Fleas become ravenously hungry, go on feeding frenzy, repeatedly biting victim, spreading disease. When too few rodents to infect, will spread to other warm-blooded hosts (e.g. humans). • If humans have lung infections (pneumonic plague), it can spread person-to-person by droplets, extremely rapid spread possible. Otherwise only by flea bites.
Stealth Attack Strategy I • Helicobacter pylori • Infects the stomach, may not cause over disease. • Can be associated with gastritis, ulcers, and gastric cancer. • Survival strategies: • Urease • Low antigenicity for Toll-like recepters • Inhibit T and B cell proliferation • Intracellular survival • Genetic rearrangement
Stealth Attack Strategy II • Salmonella typhi – Typhoid Fever • Fecal-oral transmission • Fever, headache, cramps, weakness • Carriers common with reservoirs in lymph nodes, bone marrow, etc. • Intracellular survival in macrophages • Interferon-γ helps suppress replication
Stealth Attack Strategy III • Bartonella spp. • Cat scratch fever, bacillary angiomatosis • Vector borne spread: ticks, fleas • Survival strategies: • Intracellular survival inside red blood cells • Low antigenicity • Inhibit dendritic cell maturation and T cell proliferation. • Type IV secretion system http://www.lawestvector.org/bartonella.htm http://www.emedicine.com/derm/topic44.htm
THE RACE BETWEEN MICROBES AND HOSTS CONTINUES… HOST INVASION STRATEGIES GUIDES MEDICAL INTERVENTION STRATEGIES. http://www.immunize.org/images/ca.d/ipcd1861/img0024.htm http://www.defenselink.mil/photos/Nov2004/041028-N-9864S-021.html