Comparative genomics of enterohemorrhagic Escherichia coli O145:H28 demonstrates a common evolutionary lineage with Escherichia coli O157:H7

Abstract

BackgroundAlthough serotype O157:H7 is the predominant enterohemorrhagic Escherichia coli (EHEC), outbreaks of non-O157 EHEC that cause severe foodborne illness, including hemolytic uremic syndrome have increased worldwide. In fact, non-O157 serotypes are now estimated to cause over half of all the Shiga toxin-producing Escherichia coli (STEC) cases, and outbreaks of non-O157 EHEC infections are frequently associated with serotypes O26, O45, O103, O111, O121, and O145. Currently, there are no complete genomes for O145 in public databases.ResultsWe determined the complete genome sequences of two O145 strains (EcO145), one linked to a US lettuce-associated outbreak (RM13514) and one to a Belgium ice-cream-associated outbreak (RM13516). Both strains contain one chromosome and two large plasmids, with genome sizes of 5,737,294 bp for RM13514 and 5,559,008 bp for RM13516. Comparative analysis of the two EcO145 genomes revealed a large core (5,173 genes) and a considerable amount of strain-specific genes. Additionally, the two EcO145 genomes display distinct chromosomal architecture, virulence gene profile, phylogenetic origin of Stx2a prophage, and methylation profile (methylome). Comparative analysis of EcO145 genomes to other completely sequenced STEC and other E. coli and Shigella genomes revealed that, unlike any other known non-O157 EHEC strain, EcO145 ascended from a common lineage with EcO157/EcO55. This evolutionary relationship was further supported by the pangenome analysis of the 10 EHEC str ains. Of the 4,192 EHEC core genes, EcO145 shares more genes with EcO157 than with the any other non-O157 EHEC strains.ConclusionsOur data provide evidence that EcO145 and EcO157 evolved from a common lineage, but ultimately each serotype evolves via a lineage-independent nature to EHEC by acquisition of the core set of EHEC virulence factors, including the genes encoding Shiga toxin and the large virulence plasmid. The large variation between the two EcO145 genomes suggests a distinctive evolutionary path between the two outbreak strains. The distinct methylome between the two EcO145 strains is likely due to the presence of a BsuBI/PstI methyltransferase gene cassette in the Stx2a prophage of the strain RM13514, suggesting a role of horizontal gene transfer-mediated epigenetic alteration in the evolution of individual EHEC strains.

Shiga toxins and stx phages: highly diverse entities

“…Table 1 lists stx phages whose complete sequences are available in GenBank. Recent comparisons of whole genomes have confirmed that stx phages share a general genomic organization, but with a significant degree of sequence diversity, reinforcing the concept of their mosaic nature (Ahmed et al, 2012;Smith et al 2012;Steyert et al, 2012;Cooper et al, 2014;Tozzoli et al, 2014a). Furthermore, some studies identified different types of stx phages harbouring even the same stx 2 subtype (Ahmed et al, 2012;Tozzoli et al, 2014b).…”

“…Amongst others, the gene encoding a putative DNA adenine methyltransferase has been identified in some stx phages (Cooper et al, 2014). Recently, Nübling et al…”

“…argW, potC, prfC, serU, ssrA, wrbA, yciD, yecD, yecE, yjbM, ynfH and Z2577 (Recktenwald & Schmidt, 2002;Koch et al, 2003;Ahmed et al, 2012;Steyert et al, 2012;Cooper et al, 2014).…”

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

“…The genome of VR50 had adenine methylated exclusively, with the majority (96.3%) of m6 A modifications occurring at 5=-G m6 AT C-3= deoxyadenosine methylase (Dam) motifs ( (40)(41)(42). In addition to Dam, VR50 encodes a single active type I restriction-modification (R-M) system in a typical type I operon (hsdR-hsdM-hsdS) ( Table 2).…”

An Environmental Shiga Toxin-Producing Escherichia coli O145 Clonal Population Exhibits High-Level Phenotypic Variation That Includes Virulence Traits

“…E. coli serotype O157:H7 is a prototype of EHEC and has been considered the most frequent cause of STEC-associated outbreaks; however, a growing body of evidence suggests that non-O157 STEC strains cause a large number of human infections worldwide (6)(7)(8). Several strains within serotypes O26, O103, O111, and O145 have been characterized as EHEC strains (9,10). Additionally, hypervirulent STEC strains have emerged, as exemplified by the E. coli O104:H4 strain linked to the large 2011 outbreak of hemorrhagic diarrhea in Europe.…”