Prophage induction, but not production of phage particles, is required for lethal disease in a microbiome-replete murine model of enterohemorrhagicE. coliinfection

Abstract

3Enterohemorrhagic Escherichia coli (EHEC) colonize intestinal epithelium by generating 2 4 characteristic attaching and effacing (AE) lesions. They are lysogenized by prophage that 2 5 encode Shiga toxin 2 (Stx2), which is responsible for severe clinical manifestations. As a 2 6 lysogen, prophage genes leading to lytic growth and stx2 expression are repressed, whereas 2 7 induction of the bacterial SOS response in response to DNA damage leads to lytic phage 2 8 growth and Stx2 production both in vitro and in germ-free or streptomycin-treated mice.

Pathogenomes and virulence profiles of representative big six non-O157 serogroup Shiga toxin-producing Escherichia coli

“…The most potent cytopathic toxins, Stx 2a and Stx 2d (Fuller et al, 2011;Hauser et al, 2020;McNichol et al, 2021), are prevalent in the Big Six serogroups (Jinnerot et al, 2020), and a strain's Stx-status is shaped by the dynamic Stx-phage acquisition, rather than by a common evolutionary history (Cowley et al, 2019;Nyong et al, 2020). Mobilization of Stx-prophages is triggered by diverse abiotic and biotic cues Pacheco and Sperandio, 2012), and is required to produce toxin causing adverse toxigenic effects in murine STEC models (Nguyen and Sperandio, 2012;Tyler et al, 2013;Baumler and Sperandio, 2016;Balasubramanian et al, 2019;Rodríguez-Rubio et al, 2021). Triggering the RecA-dependent SOS-response with sublethal doses of mitomycin C (MMC) constitutes a major pathway of Stx − phage mobilization and is routinely used in public health laboratories to assess the pathogenic potential (Kimmitt et al, 2000).…”