| dc.description.abstract | The microbiome is closely linked with immune homeostasis and various disease states. Chronic inflammatory diseases such as environmental enteric dysfunction (EED) and inflammatory bowel disease (IBD) are associated with general gut microbiome dysbiosis. In addition to general intestinal microbiome dysbiosis, specific enteric microbes are also implicated in the initiation or maintenance of disease states, in this case pathogenic Escherichia coli and Desulfovibrio species. A targeted reduction of these microbes without additional contribution to overall dysbiosis may serve to alleviate symptoms of chronic inflammatory disease. Bacteriophages, or simply phages, are natural predators of bacteria and, given their narrow host ranges and lytic activity, are uniquely suited for targeted modulation of the intestinal microbiome.
This work describes the development of a piglet model for E. coli-induced gastroenteritis using a chronic repeated and onetime acute dosing regimen of pathogenic E. coli in an attempt to model EED. Acute and chronic dosing regimen of E. coli-induced similar responses in interleukin-6 and interlukin-8 as well as disruptions to the resident microbiome and metabolome. Next, bacteriophages were isolated against the trial strain in an attempt to alleviate E. coli induced clinical signs. While phage efficacy for the alleviation of piglet clinical signs was inconclusive, two novel phages, Minzhu and Mangalitsa, displaying preference for low-temperatures, were isolated that may be of use for biocontrol of E. coli for food safety applications.
Given Desulfovibrio’s putative role in IBD, we sought to isolate bacteriophage infecting Desulfovibrio and evaluate their potential for applied uses. In total, six phages infecting D. desulfuricans were isolated and characterized. Growth inhibition assays showed that Desulfovibrio phages such as these may be useful in future targeted reductions of Desulfovibrio. These phages were all highly novel and represent some of the only Desulfovibrio phages isolated, sequenced, and characterized to date.
Finally, as an extension of the exploration into Desulfovibrio phages, a functional prophage element within D. desulfuricans was identified. This prophage, ProddE, along with the related Agrobacterium phage Pasto described in this work, has broad sweeping implications for the evolution and lifestyle of the paradigm phage T7 and members of the Autographiviridae. | |
