Designing a Phage Cocktail for V. cholerae O139

Abstract

Antibiotic resistance has become a crucial and increasingly common concern in the treatment of bacterial diseases. Research has additionally shown the deleterious effects of broad-use antibiotics on the human gut microbiome, which lead to illness caused by dysbiosis. Lytic bacteriophages, in contrast, can kill specific strains of bacteria using a variety of mechanisms. Phage therapy, or the treatment of bacterial disease using lytic bacteriophages, is therefore garnering attention as an alternative treatment to broad-use antibiotics. Phage cocktails, or combination treatments of specific bacteriophages, have been studied and proposed for several bacterial diseases, including cholera. Cholera is caused by strains of V. cholerae that produce cholera toxin, which typically belong to the serogroups O1 or O139. No cocktails have been proposed targeting strains of the O139 serogroup. Using the host ranges of previously isolated and reported bacteriophages, this thesis employs a combinatorial approach to design a phage cocktail for V. cholerae O139. The cocktail proposed contains the phages JSF-3, ØVC1, MAD-5, VE-2, and S-2, and it theoretically lyses at least different 57 strains of V. cholerae O139. Furthermore, the genetic and structural properties of the collected bacteriophages show that the proposed phage cocktail consists of phages that are diverse in adsorption, replication, and cell killing mechanisms. Future research is required to test the hypothetical cocktail in animal models to determine its efficacy and to test for any harmful side effects caused by the treatment.