animal- and arthropod-transmitted diseases › courses › biological-engineering › 20...animal-...
TRANSCRIPT
Animal- and arthropod-transmitteddiseases
Dec 6, 2006Ch. 27
Galán and Wolf-Watz review
Plague
• Infectious disease of animals and humans• Caused by a bacterium named Yersinia
pestis• People usually get plague from being bitten
by a rodent flea that is carrying the plaguebacterium
• Antibiotics are effective against plague,but if an infected person is not treatedpromptly, the disease is likely to causeillness or death
Epidemiology
• Wild rodents incertain areas areinfected with plague
• Outbreaks usuallyassociated withinfected rats and ratfleas (Xenopsyllacheopis)
• Globally, the WHOreports 1,000 to 3,000cases of plague eachyear
http://www.cdc.gov/ncidod/dvbid/plague
History of plague
• First pandemicspread from Egyptto Europe, Africa,and Asia 542-600
• Second pandemicknown as the BlackDeath spread fromAsia to Europe inthe 1300s
http://bubonicplague.quickseek.com/
Natural history• Epidemics usually involve
rats• Last rat-borne epidemic in
the US occurred in LosAngeles in 1924-25
• Since then, all human casesin the U.S. have beensporadic cases acquiredfrom wild rodents
• Rock squirrels and theirfleas are the mostfrequent sources of humaninfection in thesouthwestern states www.mammalogy.org
Courtesy of Diliff.
Geographic distribution
• Averages about 18cases per year in US
• Mostly in people < 20years of age
• About 1 in 7 personswill die
• Epidemic plague occursAfrica, Asia, & SouthAmerica associatedwith domestic rats
Forms of disease• Bubonic plague
– enlarged, tender lymph nodes,fever, chills and prostration
• Septicemic plague– fever, chills, prostration,
abdominal pain, shock andbleeding into skin and otherorgans
• Pneumonic plague– fever, chills, cough and
difficulty breathing; rapidshock and death if not treatedearly www.cdc.gov/ncidod/dvbid/plague
Diagnosis of plague• Painful, swollen lymph node, called a bubo• Onset usually 2-6 days after exposure• Disease progresses rapidly and bacteria
invade the bloodstream, producing severeillness, called plague septicemia
• Progression leads to lung infection orplague pneumonia
• Incubation period of primary pneumonicplague is 1-3 days– Characterized by overwhelming pneumonia with
high fever, cough, bloody sputum, and chills– Mortality rate > 50%
Treatment
• As soon as a diagnosis of suspected plagueis made, the patient should be isolated, andlocal and state health departments shouldbe notified
• The drugs of choice are streptomycin orgentamicin, but a number of otherantibiotics are also effective
• Those individuals closely associated withthe patient, particularly in cases withpneumonia, should be traced, identified,and evaluated
Prevention• Epidemic plague is best prevented by
controlling rat populations in bothurban and rural areas
• In regions where plague is widespreadin wild rodents, the greatest threat isto people living, working, or playing inareas where the infection is active– Eliminate food and shelter for rodents– Surveillance in wild rodent populations– Use of appropriate insecticides to kill
fleas
The bacterium
• Gram negative facultative anaerobe• Formerly classified in the family
Pasteurellaceae, but based on DNA-DNA hybridization member of theEnterobacteriaceae family
• 11 named species, but only 3 arehuman pathogens– Y. pestis, the etiologic agent of plague– Y. pseudotuberculosis and Y.
enterocolitica
http://www.cdc.gov/ncidod/dvbid/plague
Zhou et al. Microbes Infect 6:1226-34, 2004.
Diagram removed due to copyright restrictions.
Invasion
• EnteropathogenicYersinia speciesinvade culturedmammalian cells
• Mediated by invgene productinvasin
• Outer membraneprotein binds β1integrins
Isberg and Barnes, J Cell Sci 114:21-28, 2001.
Figure by MIT OCW.
Bacterium Bacterium Bacterium
No Signaling
Signaling
Signaling
Invasin
Integrin
D2
A. Low substrate density B. High substrate density C. Substrate dimerization
Neutra et al. Nature Immunol 2:1004-9, 2001.
Image removed due to copyright restrictions.
Hu et al. J Bacteriol 180:5192-5202, 1998
rep region
0
Transposase
ColE1 replicon Pesticinimmunityprotein
Pesticin Plasminogenactivator
40001000 2000 3000 5000 6000 7000 8000 9000 10000
caf1M
caf1R ORF4
T3 ligase
IS100
IS100
ORF135
ORF131
antirestriction
ORF127
ORF125ORF126
ORF123Amethylase
ORF122
ORF119
ORF116
ORF115A
ORF115 parB
parA
ORF110ORF11
2ORF11
2Ares
olvase
ORF1
09OR
F108
mur
ine t
oxin
ORF
106A
ORF
106
ORF
105
ORF
104
ORF
103A
ORF
103
ORF
102
IS28
5O
RF1
00
OR
F99
IS100
OR
F98 O
RF96
OR
F97 O
RF95
IS100IS100
lambda G
-like O
RF91A
lambda ORF314-like
ORF90
lambda J-like
lambda K-like
lambda I-like
lambda H-like
lambda M-like
lambda V-like
lambda L-like
ORF80ORF81ORF82
ORF71ORF72ORF73ORF74AL12-likeORF76ORF77ORF78
ORF70
T4 gene 17-like
ORF64ORF65
ORF66
ORF68
ABC transporter-like
Spo J-likeRep-like
ORF54
ORF55
ORF57
ORF58
ORF59rep
ressor-li
ke
ORF44
ORF45
ORF48
ORF51
ORF53
ORF47
IS20
0
exoA
exoB
ORF
36O
RF38
ORF
39
ORF4
2
repAOR
F33A
OR
F33OR
F32O
RF31O
RF29
HflC
-like
recA
ORF25
ORF23
pprB-like
ORF21
ORF18
ORF17
DNA pol III
cobScobT
ORF14ORF13integrase
caf1
caf1A
10000
2000030000
40000
5000060000
7000
080
000
90000
100000
pMT1
lambd
a-like
Figure by MIT OCW.
Jarrett et al. J Infect Dis 190:783-92, 2004.
Images removed due to copyright restrictions.
Hu et al. J Bacteriol 180:5192-5202, 1998
Image removed due to copyright restrictions.
Cornelis Nature Rev Mol Cell Biol 3:742-754, 2002
Images removed due to copyright restrictions.Figures 1 and 2 in "THE YERSINIA YSC–YOP 'TYPE III' WEAPONRY," Nature Reviews Molecular Cell Biology 3, 742-754 (2002).