Abstract
Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated.
Highlights
Prophages are bacteriophage genomes that replicate alongside their bacterial host’s genome until induced to produce viral particles
From the American Type Culture Collection (ATCC—identifier ATCC43895) we acquired the Shiga toxin-producing microorganisms like Escherichia coli (STEC) serotype O157:H7 whose genome sequence is published under strain EDL933 [11,12]
The (point primary regarding theprophage potential for using phage therapy to treat pathogenic standard route is through induction, resulting in Shiga toxin (Stx) gene lysogens is whether such treatment might exacerbate patient exposure to toxins produced expression followed by Shiga toxin release via phage-induced bacterial lysis [20,38]
Summary
Prophages are bacteriophage (phage) genomes that replicate alongside their bacterial host’s genome until induced to produce viral particles. This carriage state, termed a lysogenic cycle, is characteristic of temperate phages (as opposed to strictly lytic, or virulent, phages), and the prophagecarrying bacterial host is termed a lysogen. One impact of temperate phage biology is lysogenic conversion: the modification of a host phenotype by prophage genes, including genes encoding bacterial virulence factors [4,5,6]. Notable among prophage-encoded virulence factors are exotoxins, such as those associated with the O157:H7 serotype of Shiga-toxigenic Escherichia coli (STEC) [7].
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