ugpn ritchie.ppt [modo de compatibilidade] · 2012. 4. 3. · pseudomonas sp. vibrio spp. neisseria...
TRANSCRIPT
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Jennifer Ritchie, PhD
Lecturer in Microbial PathogenesisUniversity of Surrey
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Faculty of Health and Medical Sciences (FHMS)
bacterial pathogenesis
Institute ofBiosciences
andMedicine
microbial &cellular sci.
biochemistry& physiology
nutrition & metabolism
surrey clinicalresearch ctr
virologysystems biology oncology
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Pathogenesis – the cellular events and processes that occur during the development of a disease
Bacterial pathogens that are studied include:
pathogenic E. coli (enterohaemorrhagic, avian)
Salmonella
Campylobacter jejuni
Mycobacterium tuberculosis
Pseudomonas sp.
Vibrio spp.
Neisseria meningitidis
Roberto LaRagione
Graham Stewart
Simon Park
Johnjoe McFadden
zoon
otic
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Pathogenic E. coli1) Enterohaemorrhagic E. coli (EHEC)
main reservoir of EHEC
E. coli O104:H4
Predominant serotypeE. coli O157:H7
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ingestion of contaminatedfood / water
survive acidic milieu of upper GI tract
colonize lower GI tract
interaction of Stx with receptor on target cells
host cell deathand kidney failure
Shiga toxin translocation across gut epithelium
EHEC shed in stool
An non‐invasive enteric pathogen….
lumen
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identification of specific colonization factors
• e.g. espFu, long polar fimbriae
basic research translational studies
O157‐specifc pyocin
testing of an O157‐specific pyocin to reduce fecal shedding
identification of infection‐linked changes in the E. coli O157:H7 transcriptome
characterization of the role of quorum sensing in EHEC pathogenesis
using small molecule inhibitors to block EHEC communication
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Pathogenic E. coli2) Avian E.coli (APEC)
• Extraintestinal E. coli (ExPEC) – organisms cause infections outside of normal intestinal inhabitat ie urinary tract infections, newborne meningitis
• APEC causes a complex of systemic infections, mainly respiratory disease, in poultry
• Similarity between APEC and other ExPEC of human and animal origin suggests a zoonotic link between populations
• Possibility that retail chicken may be important reservoir for E. coli causingExPEC infections in humans
Studies are underway to identify key factors that affect the ‘survival fitness’ and virulence of various APEC strains isolated from diseased chickens.
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Haiti (2010):>325,000 cases>5,000 deaths
Pathogenic Vibrio species1) Vibrio cholerae
• causes the devastating diarrhealdisease, cholera
• natural inhabitant of marine / estuarine environments
• highly motile bacterium
Adapted from Butler and Camilli
lifecycle of V. cholerae
• infection occurs following ingestion of contaminated water
• cholera toxin is largely responsible for the development of diarrhea
• studied for more than 100 years, but little is known about cholera transmission
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Transmission of V. cholerae
Primary host Secondary hosts
Secondary transmission
INDIRECTvia contaminated water
Environmental reservoir
(low levels of V. choleraerecovered by standardculture techniques)
rapid rise in number of
infected individuals“explosive nature of cholera epidemics”
DIRECTPrimary
transmission ‘person‐to‐person’
• Passage through the intestine increases the virulence of V. cholerae, but the molecular mechanism(s) that explain this phenomena are poorly understood.• Using an animal model of cholera transmission, we are beginning to investigate this question.
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• Leading cause of bacterial gastroenteritis associated with consumption of raw or undercooked seafood
• Infected individuals develop self‐limiting gastroenteritis, characterized by diarrhea, abdominal pain and fever
• One of largest outbreaks occurred in Chile in 2005 wheremore 10,000 individuals were affected
Pathogenic Vibrio species2) Vibrio parahaemolyticus
• Natural inhabitant of marine environment, most commonly isolated in warmerseawaters (e.g. Southeast Asia)
• Little is known about how this bacterium causes intestinal disease
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• We developed an animal model to study the infection processes
• Our studies suggest that V. parahaemolyticus follows an organized series of stepsincluding attachment, remarkable elongation of microvilli and the formation ofV. parahaemolyticus‐filled cavities within the epithelial surface and culminates invillus disruption
• Future studies aim to identify the bacterial factors and cellular processes that contribute to intestinal disease
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Thank you for your attention