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Dynamics of epidemic V. cholerae O1 and vibriophage concentration in surface water during a cholera epidemic in Bangladesh. Dynamics of epidemic V. cholerae O1.

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Presentation on theme: "Dynamics of epidemic V. cholerae O1 and vibriophage concentration in surface water during a cholera epidemic in Bangladesh. Dynamics of epidemic V. cholerae O1."— Presentation transcript:

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2 Dynamics of epidemic V. cholerae O1 and vibriophage concentration in surface water during a cholera epidemic in Bangladesh. Dynamics of epidemic V. cholerae O1 and vibriophage concentration in surface water during a cholera epidemic in Bangladesh. Weekly mean V. cholerae O1 levels (A) and lytic vibriophage levels (B) in the aquatic environment were taken during the course of a cholera epidemic in Bangladesh. Environmental sampling was conducted from the third week of August to the third week of December The number of cholera patients are extrapolated from 2% surveillance samples. Dynamics of epidemic V. cholerae O1 and vibriophage concentration in surface water during a cholera epidemic in Bangladesh. Weekly mean V. cholerae O1 levels (A) and lytic vibriophage levels (B) in the aquatic environment were taken during the course of a cholera epidemic in Bangladesh. Environmental sampling was conducted from the third week of August to the third week of December The number of cholera patients are extrapolated from 2% surveillance samples. Shah M. Faruque et al. PNAS 2005;102: ©2005 by National Academy of Sciences

3 Schematic model for factors influencing seasonal epidemics of cholera.
Schematic model for factors influencing seasonal epidemics of cholera. Events occurring in the environment are shown in circles, whereas those occurring in human cholera victims are shown in rectangles. 1, Seasonal conditions (e.g., floods or physical-chemical factors causing phage instability) lead to the reduction of viable lytic phages in the aquatic environment. 2, Other seasonal factors (e.g., elevated temperature or biological-cofactors) lead to a bloom of nonpathogenic and pathogenic Vibrio species in local water sources. 3, A favorable aquatic environment facilitates infection by a pathogenic V. cholerae strain (black vibrios), causing an asymptomatic or undetected symptomatic infection in an index case. 4, Amplification of the pathogenic clone in the index case seeds the environment. 5, An epidemic begins, triggered by the index case leading to host amplification of the pathogenic clone and massive environmental contamination. 6, Phages produced by environmental Vibrio species (e.g., through induction of lysogens or lytic growth) begin to amplify on the pathogenic clone in the environment. 7, Cholera victims increasingly ingest both the pathogenic clone and the lytic phage from environmental sources leading to amplification of the phage in vivo. 8, Environmental contamination with phage shed by cholera victims and further amplification of phage on the pathogenic clone within the environment lead to collapse of the epidemic. Factors contributing to the collapse of the epidemic include the decreasing concentration of the pathogenic clone in the environment coincident with a upsurge in environmental phage concentration that together contribute to a dramatic reduction in the rate of transmission of cholera in the interepidemic period. Schematic model for factors influencing seasonal epidemics of cholera. Events occurring in the environment are shown in circles, whereas those occurring in human cholera victims are shown in rectangles. 1, Seasonal conditions (e.g., floods or physical-chemical factors causing phage instability) lead to the reduction of viable lytic phages in the aquatic environment. 2, Other seasonal factors (e.g., elevated temperature or biological-cofactors) lead to a bloom of nonpathogenic and pathogenic Vibriospecies in local water sources. 3, A favorable aquatic environment facilitates infection by a pathogenicV. cholerae strain (black vibrios), causing an asymptomatic or undetected symptomatic infection in an index case. 4, Amplification of the pathogenic clone in the index case seeds the environment. 5, An epidemic begins, triggered by the index case leading to host amplification of the pathogenic clone and massive environmental contamination. 6, Phages produced by environmental Vibrio species (e.g., through induction of lysogens or lytic growth) begin to amplify on the pathogenic clone in the environment. 7, Cholera victims increasingly ingest both the pathogenic clone and the lytic phage from environmental sources leading to amplification of the phage in vivo. 8, Environmental contamination with phage shed by cholera victims and further amplification of phage on the pathogenic clone within the environment lead to collapse of the epidemic. Factors contributing to the collapse of the epidemic include the decreasing concentration of the pathogenic clone in the environment coincident with a upsurge in environmental phage concentration that together contribute to a dramatic reduction in the rate of transmission of cholera in the interepidemic period. Shah M. Faruque et al. PNAS 2005;102:

4 six bacteriopha ges (BC-BP-01 to BC-BP-06,
Test material contained 100 000 plaque-forming units (PFU; standardised at the date of manufacture) of each of six bacteriophages (BC-BP-01 to BC-BP-06 NCIMB deposit numbers 41174–41179) a common gram-negative rod-shapedbacterium that can cause diseases in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a prototypical "multidrug resistant (MDR) pathogen"  deposit numbers 41174–41179) NCIMB six bacteriopha ges (BC-BP-01 to BC-BP-06, Test material contained plaque-forming units (PFU; standardised at the date of manufacture) of each of 15

5 - Good Manufacturing Practice

6 Random Amplified Polymorphic DNA

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9 Phagoburn is a European Research & Development (R&D) project funded by the European Commission under the 7th framework program for R & D. The project was launched on June 1st 2013 and will last 45 months. It aims at evaluating  phage therapy for the treatment of burn wounds infected with bacteriaEscherichia coli and Pseudomonas aeruginosa. This evaluation is currently running through the implementation of a phase I-II clinical trials. In addition, results obtained within Phagoburn will contribute to provide basis for an optimisation of current regulatory guidelines in phage therapy.

10 Klebsiella pneumoniae is a gram-negative, nonmotile, facultative, rod-shaped  bacterium. Although found in the normal flora of the mouth, skin, and intestines, it can cause destructive changes to human and animal lungs if aspirated (inhaled), specifically to the alveoli…  Figure 1. Morphology of phages as revealed by TEM. Three phages displayed different morphology. GH-K2 displayed a short and contractile tail. The tails of GH-K1 and GH-K3 were long, and the tail of GH-K3 appeared more flexible than that of GH-K1. The bars represent 200 nm. Gu J, Liu X, Li Y, Han W, Lei L, et al. (2012) A Method for Generation Phage Cocktail with Great Therapeutic Potential. PLOS ONE

11 Table 1. Susceptibility of strains to different phages.
Gu J, Liu X, Li Y, Han W, Lei L, et al. (2012) A Method for Generation Phage Cocktail with Great Therapeutic Potential. PLOS ONE

12 In the present study, we report a SBS method
In the present study, we report a SBS method. The method takes advantage of the occurrence of phage-resistant variants and ensures phages lytic for wild-type strain and its phage-resistant variants are selected. The phage cocktail established by this method can not only display broad lytic range, but also ensure that bacteria resistant to one phage remain susceptible to others. Hence, the cocktail established by SBS is significantly different from previous phage cocktails  Figure 3. Survival rate of bacteremic mice treated with different doses of phages. Mice were inoculated intraperitoneally with K7 at the dose of 2.5×108 cfu. Thirty minutes later, different doses of GH-K1 (○), GH-K2 (□), GH-K3 (Δ), or phage cocktail (◊) were injected into the peritoneal cavity of the mice. Every group contained five mice and each symbol represents the average of three experiments. The error bars indicate SD. Gu J, Liu X, Li Y, Han W, Lei L, et al. (2012) A Method for Generation Phage Cocktail with Great Therapeutic Potential. PLOS ONE


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