Download Wk1- FrontalStealth

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.
Vibrio cholera toxin (CT) regulation:
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.
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 personto-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
http://www.hi-tm.com/Documents/Handwash-FL99.html
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
Figures from:
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