Abstract
Salmonella Typhimurium is one of the leading causes of food borne illness worldwide. Member of the gram negative Enterobacteriaceae family, Salmonella can become harmful to the host when it blooms in the gut and causes inflammation. Some Enterobacteriaceae secrete microcins, which are small antimicrobial peptides that compete for resources within their environment, targeting competitors for elimination, thus preventing overpopulation of pathogenic strains such as Salmonella. Narrow spectrum microcins may be able to alleviate incidence of Salmonella and intestinal dysbiosis. One such microcin is H47. It was hypothesized that E. coli Nissle produces an immature microcin H47, via its chromosomal gene, mchB, but does not produce mature microcin H47, as it lacks a necessary posttranslational modifier, mchA. Previous work has shown that supplementing Nissle with its chromosomal microcin gene cluster in addition to mchA results in inhibition of Salmonella Typhimurium. However, since most of the genes in this plasmid-based system are already present in the chromosome of Nissle, my goal was to determine the minimal components necessary for Nissle-mediated inhibition of Salmonella Typhimurium. I created different constructs and tested their antimicrobial potency in Nissle against E. coli strain DH5 and Salmonella Typhimurium. When tested against Salmonella, Nissle wildtype did not show inhibitory activity, both Nissle with mchA and Nissle with mchB showed similarly minimal levels of inhibition, and Nissle with both mchA and mchB showed the greatest inhibition. Future work could involve making minimal modifications to Nissle's genome to give the already-commercially-available probiotic the capacity to inhibit Salmonella. If successful, the modified probiotic could then be used as a prophylactic measure and other strains could also be engineered in similar ways for targeted eradication of pathogens, potentially including those that are multi-drug resistant.