Bacteriophages of Shiga Toxin-Producing Escherichia coli and Their Contribution to Pathogenicity

Abstract

Shiga toxins (Stx) of Shiga toxin-producing Escherichia coli (STEC) are generally encoded in the genome of lambdoid bacteriophages, which spend the most time of their life cycle integrated as prophages in specific sites of the bacterial chromosome. Upon spontaneous induction or induction by chemical or physical stimuli, the stx genes are co-transcribed together with the late phase genes of the prophages. After being assembled in the cytoplasm, and after host cell lysis, mature bacteriophage particles are released into the environment, together with Stx. As members of the group of lambdoid phages, Stx phages share many genetic features with the archetypical temperate phage Lambda, but are heterogeneous in their DNA sequences due to frequent recombination events. In addition to Stx phages, the genome of pathogenic STEC bacteria may contain numerous prophages, which are either cryptic or functional. These prophages may carry foreign genes, some of them related to virulence, besides those necessary for the phage life cycle. Since the production of one or more Stx is considered the major pathogenicity factor of STEC, we aim to highlight the new insights on the contribution of Stx phages and other STEC phages to pathogenicity.

Variability in the Occupancy of Escherichia coli O157 Integration Sites by Shiga Toxin-Encoding Prophages

“…Indeed, the presence of non-Stx prophages was documented. While they were suggested to represent either complete, inducible phages or non-inducible, remnant, cryptic or residual phages [ 35 ], their role in pathogenesis is not clear and likely differs across strains. In the O157 Sakai genome, for instance, 18 distinct prophages were identified; most contained numerous genetic defects, though some were inducible [ 36 ].…”

“…The increased number of occupied Stx-encoding bacteriophage insertion sites relative to the number of Stx prophages further highlights the plasticity of the E. coli O157 genome and a divergent evolutionary trend of this pathogen. Prior studies documented recombination between prophages within the same bacterial genome [ 32 , 37 ], which was suggested to occur between homologous regions among co-existing prophages [ 35 ]. However, differentiating between these Stx and non-Stx prophages using whole-genome sequencing is difficult given that contig assembly programs cannot always distinguish them from each other [ 35 ].…”

“…Prior studies documented recombination between prophages within the same bacterial genome [ 32 , 37 ], which was suggested to occur between homologous regions among co-existing prophages [ 35 ]. However, differentiating between these Stx and non-Stx prophages using whole-genome sequencing is difficult given that contig assembly programs cannot always distinguish them from each other [ 35 ]. Through the use of multiple PCR-based assays described herein, we were able to determine which insertion sites harbored the Stx genes in most of the strains examined.…”

Interactions of Bacteriophages with Animal and Human Organisms—Safety Issues in the Light of Phage Therapy

“…It was also observed that the oral administration of phages could alter microbiota even in healthy individuals. This has led to a concept of phages as mammalian pathogens that can be a source of infection [133,169,170]. Phage DNA and RNA act as inflammatory agents that trigger immune response [171].…”

The Repressor C Protein, Pf4r, Controls Superinfection of Pseudomonas aeruginosa PAO1 by the Pf4 Filamentous Phage and Regulates Host Gene Expression

“…Bacteriophages are important factors in the diversification of bacterial species. In Corynebacterium diphtheriae and Escherichia coli O157, prophages, bacteriophage integrated into the host chromosome and are replicated as part of the host, have been shown to harbour genes that encode toxins and virulence factors, enhancing the pathogenicity of the host bacterium [ 1 , 2 , 3 ]. Endogenous oxidative stress in biofilms is also known to drive diversity in biofilm communities [ 4 ].…”