Jennifer Ritchie, PhD

Transcription

1 Jennifer Ritchie, PhD Lecturer in Microbial Pathogenesis University of Surrey

2 Faculty of Health and Medical Sciences (FHMS) Institute of Biosciences and Medicine microbial & cellular sci. biochemistry & physiology nutrition & metabolism surrey clinical research ctr virology systems biology oncology bacterial pathogenesis

3 Pathogenesis the cellular events and processes that occur during the development of a disease Bacterial pathogens that are studied include: zoonotic pathogenic E. coli (enterohaemorrhagic, avian) Salmonella Campylobacter jejuni Roberto LaRagione Mycobacterium tuberculosis Pseudomonas sp. Simon Park Vibrio spp. Neisseria meningitidis Graham Stewart Johnjoe McFadden

4 Pathogenic E. coli 1) Enterohaemorrhagic E. coli (EHEC) Predominant serotype E. coli O157:H7 main reservoir of EHEC E. coli O104:H4

5 An non invasive enteric pathogen. ingestion of contaminated food / water survive acidic milieu of upper GI tract colonize lower GI tract Shiga toxin translocation across gut epithelium EHEC shed in stool lumen interaction of Stx with receptor on target cells host cell death and kidney failure

6 basic research identification of specific colonization factors e.g. espfu, long polar fimbriae translational studies testing of an O157 specific pyocin to reduce fecal shedding O157 specifc pyocin characterization of the role of quorum sensing in EHEC pathogenesis identification of infection linked changes in the E. coli O157:H7 transcriptome using small molecule inhibitors to block EHEC communication

7 Pathogenic E. coli 2) 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 causing ExPEC 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.

8 Pathogenic Vibrio species 1) Vibrio cholerae causes the devastating diarrheal disease, cholera natural inhabitant of marine / estuarine environments highly motile bacterium Haiti (2010): >325,000 cases >5,000 deaths infection occurs following ingestion of contaminated water cholera toxin is largely responsible for the development of diarrhea Adapted from Butler and Camilli lifecycle of V. cholerae studied for more than 100 years, but little is known about cholera transmission

9 Transmission of V. cholerae Primary host Primary transmission Environmental reservoir Secondary transmission DIRECT person to person Secondary hosts (low levels of V. cholerae recovered by standard culture techniques) INDIRECT via contaminated water rapid rise in number of infected individuals explosive nature of cholera epidemics 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.

10 Pathogenic Vibrio species 2) Vibrio parahaemolyticus Natural inhabitant of marine environment, most commonly isolated in warmer seawaters (e.g. Southeast Asia) 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 where more 10,000 individuals were affected Little is known about how this bacterium causes intestinal disease

11 We developed an animal model to study the infection processes Our studies suggest that V. parahaemolyticus follows an organized series of steps including attachment, remarkable elongation of microvilli and the formation of V. parahaemolyticus filled cavities within the epithelial surface and culminates in villus disruption Future studies aim to identify the bacterial factors and cellular processes that contribute to intestinal disease

12 Thank you for your attention