Comparison of Shiga toxin-encoding bacteriophages in highly pathogenic strains of Shiga toxin-producing Escherichia coli O157:H7 in the UK

Abstract

Over the last 35 years in the UK, the burden of Shiga toxin-producing <i>Escherichia coli</i> (STEC) O157:H7 infection has, during different periods of time, been associated with five different sub-lineages (1983-1995, Ia, I/IIa and I/IIb; 1996-2014, Ic; and 2015-2018, IIb). The acquisition of a <i>stx2a</i>-encoding bacteriophage by these five sub-lineages appears to have coincided with their respective emergences. The Oxford Nanopore Technologies (ONT) system was used to sequence, characterize and compare the <i>stx</i>-encoding prophages harboured by each sub-lineage to investigate the integration of this key virulence factor. The <i>stx2a</i>-encoding prophages from each of the lineages causing clinical disease in the UK were all different, including the two UK sub-lineages (Ia and I/IIa) circulating concurrently and causing severe disease in the early 1980s. Comparisons between the <i>stx2a-</i>encoding prophage in sub-lineages I/IIb and IIb revealed similarity to the prophage commonly found to encode <i>stx2c</i>, and the same site of bacteriophage integration (<i>sbcB</i>) as <i>stx2c</i>-encoding prophage. These data suggest independent acquisition of previously unobserved <i>stx2a</i>-encoding phage is more likely to have contributed to the emergence of STEC O157:H7 sub-lineages in the UK than intra-UK lineage to lineage phage transmission. In contrast, the <i>stx2c</i>-encoding prophage showed a high level of similarity across lineages and time, consistent with the model of <i>stx2c</i> being present in the common ancestor to extant STEC O157:H7 and maintained by vertical inheritance in the majority of the population. Studying the nature of the <i>stx</i>-encoding bacteriophage contributes to our understanding of the emergence of highly pathogenic strains of STEC O157:H7.