Prophage Induction Is Enhanced and Required for Renal Disease and Lethality in an EHEC Mouse Model

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS Pathogens (Impact Factor: 7.56). 03/2013; 9(3):e1003236. DOI: 10.1371/journal.ppat.1003236
Source: PubMed


Author Summary
Infection with Enterohemorrhagic E. coli (EHEC), and more recently with the Enteroaggregative E. coli strain O104:H4, is a significant health risk, causing bloody diarrhea, kidney failure, and even death. The virulence factor in these bacteria responsible for the severe outcomes is Shiga toxin (Stx). Genes encoding Stx are in the genome of bacterial viruses (prophages) on the pathogenic E. coli chromosomes. The prophage remains quiescent until damage to the bacterial chromosome occurs causing prophage gene expression (called induction), which leads to production of bacteriophages that are released into the environment. Because stx expression is controlled by the phage regulatory system, prophage induction leads additionally to production and release of Stx. This study provides conclusive evidence that in a mouse model of EHEC infection, induction of the prophage carrying the stx genes is specifically required for EHEC to cause disease and that the intestinal environment adds to the induction and therefore to the production of Stx. Similar events likely regulate Stx production and release by the Stx encoding phage in the O104:H4 strain. Controlling prophage induction offers a means to control EHEC infection.

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Available from: Karen Beeri, Mar 03, 2015
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    • "The life cycle of prophages is controlled by phage repressor CI proteins in lambdoid phage (Ptashne and Hopkins, 1968). Mutations in the cI gene make a non-cleavable repressor and an uninducible 933W Stx2 prophage (Tyler et al., 2013). RecA can stimulate the self-cleavage of CI further allowing initiation of transcription from the early P L and P R promoters (Little, 2005). "
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    • "induction is critical to Stx gene expression and to the ability of STEC to cause disease (Tyler et al., 2013). The toxin genes are late-stage genes that are transcribed only during the lytic stage of the phage. "
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    International journal of medical microbiology: IJMM 03/2015; 305(3). DOI:10.1016/j.ijmm.2015.02.002 · 3.61 Impact Factor
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    • "Analysis of colonoscopy biopsies have shown that the mucus of Crohn's disease patients was 30-fold enriched in virus-like particles (3 × 10 9 VLP/biopsy versus 10 8 for healthy controls (Lepage et al., 2008). Even in the absence of external signal or inflammation, the stx2 carrying E. coli prophage 933 W is more induced in the gut of monoxenic mice than in vitro (Tyler et al., 2013). In E. coli and Lactobacillus genomes, the vast majority of prophages are defective, indicating an active selection against prophages induction (Martin et al., 2009). "
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