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1 December 2008 Using Bacteriophages to Modulate Salmonella Colonization of the Chicken's Gastrointestinal Tract: Lessons Learned from In Silico and In Vivo Modeling
A. Hurley, J. J. Maurer, M. D. Lee
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An increasing prevalence of antibiotic-resistant foodborne infections has resulted in considerable concern about how antimicrobials are used in meat and poultry production. Because many foodborne bacterial pathogens are commonly found among the intestinal bacterial community of poultry, new methods of prevention are being considered. Bacteriophage therapy is one such alternative method that has not been well developed in the United States; however, bacteriophages have been shown to be effective in modulating bacterial numbers in acute infection models. In this study we evaluated whether bacteriophages could theoretically reduce Salmonella colonization of the gastrointestinal tract of chickens. Using computer simulations, we studied bacteriophage and bacterial replication dynamics in a mathematical model based on parameters expected to occur in the intestinal environment. In addition, we performed in vivo experiments by administering SP6 bacteriophage and Salmonella orally to young chickens and compared the levels of phage and Salmonella shed in the feces to the models of replication dynamics. SP6 is an ideal candidate bacteriophage because its genome and target receptor are known. Although SP6 did not reduce the levels of Salmonella shed by treated birds, most of the isolates recovered from treated birds were not resistant to the bacteriophage. These results suggest that phage resistance may not be the primary limiting parameter of phage prophylaxis for modulating colonization of the intestine. Our findings that this phage could be replicated in vivo supports the attractiveness of phage use, because unlike antibiotics they may be amplified in vivo if given a suitable host on which to replicate. If successful, this approach to modulating bacterial colonization of the intestinal tract could have a tremendous effect on the meat and poultry industry by reducing the use of antimicrobial drugs and increasing the use of biological therapeutics.

Abbreviations: BHI = brain heart infusion; bp = base pair; cfu = colony-forming units; LPS = lipopolysaccharide; PCR = polymerase chain reaction; pfu = plaque-forming units

Uso de bacteriófagos para modular la colonización de Salmonella en el tracto gastrointestinal de los pollos: Lecciones aprendidas con los modelos In Silico e In Vivo

El incremento en la prevalencia de la resistencia a los antibióticos en infecciones originadas en los alimentos ha resultado en una considerable preocupación acerca de la forma como los antimicrobianos son usados en la producción de carne. Debido a que muchos patógenos bacterianos son comúnmente encontrados entre la comunidad bacteriana de las aves, se están considerando nuevos métodos de prevención. La terapia con bacteriófagos es uno de los métodos alternos que no se han desarrollado bien en los Estados Unidos; sin embargo, los bacteriófagos han mostrado su efectividad en la modulación del número de bacterias en modelos de infecciones agudas. En este estudio evaluamos si los bacteriófagos pueden teóricamente reducir la colonización con Salmonella del tracto gastrointestinal de los pollos. Usando simulaciones computarizadas, estudiamos los bacteriófagos y la dinámica de replicación de las bacterias en un modelo matemático basado en parámetros que se espera ocurran en el ambiente intestinal. Adicionalmente, desarrollamos experimentos in vivo administrando bacteriófago SP6 y Salmonella oralmente a pollitos jóvenes y se compararon los niveles de fagos y Salmonella eliminados en las heces con los modelos de las dinámicas de replicación. El bacteriófago SP6 es un candidato ideal porque su genoma y su receptor objetivo son conocidos. Aunque

A. Hurley, J. J. Maurer, and M. D. Lee "Using Bacteriophages to Modulate Salmonella Colonization of the Chicken's Gastrointestinal Tract: Lessons Learned from In Silico and In Vivo Modeling," Avian Diseases 52(4), 599-607, (1 December 2008).
Received: 19 March 2008; Accepted: 1 July 2008; Published: 1 December 2008

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