ST131 belongs to the
E. coli phylogenetic group B2, which encompasses the largest group of
E. coli associated with extra-intestinal infections. Based on phylogenetic analyses, the ST131 strains EC958, NA114 and JJ1886 cluster together in a clade discrete from SE15, and separate from representative strains from other
E. coli phylogroups (
Figure 1). Two recent studies have independently examined the global epidemiology of ST131 using genome sequence-based methods [
18,
19]. These studies identified a globally dominant fluoroquinolone resistant-FimH30 sub-lineage defined as
H30 [
18] or clade C [
19]. All strains within this sub-lineage possessed the fluoroquinolone resistance alleles
gyrA1AB and
parC1aAB. Further analysis also revealed that ST131 strains containing the
blaCTX-M-15 allele comprised a smaller subset of strains within this sub-lineage and were referred to as
H30-Rx [
18] or clade C2 [
19]. Strikingly, the data from both studies supports the recent emergence and global dissemination of this sub-lineage from a single progenitor, provoking intriguing questions with respect to ST131 transmission, colonization and virulence.
In addition to the dominant clade C that comprised 79% of our sequenced ST131 strains, our analysis also identified two other well-supported ST131 clades referred to as A and B [
19]. Clade A, represented by the reference strain SE15, was the most divergent and comprised strains that contained the
fimH41 allele. In contrast, strains from clade B were very similar to those from clade C and characterised by possession of the
fimH22 allele. The prevalence of these
fimH alleles, including the dominant
H30 allele, is consistent with that reported previously from a large and extensive collection of ST131 strains [
13].
Figure 1.
Maximum likelihood phylogenetic comparison of ST131 strains EC958, JJ1886, NA114 (clade C) and SE15 (clade A), and 16 representative strains from other
E. coli phylogroups. The phylogenetic relationships were inferred with the use of 70,777 SNPs identified between the genomes of the 20
E. coli strains and 1000 bootstrap replicates. The major
E. coli phylogroups are coloured as follows; group B2-ST131: (red); group B2 non-ST131: APEC-01, S88, 536, UTI89, CFT073, ED1A (orange); group D: UMN026, IAI39 (yellow); group A: BW2952, MG1655, W3110, HS (green); group B1: SE11, IAI1 (aquamarine); group E: O157 EDL933, O157 Sakai (blue). Nodes are coloured according to bootstrap support for branching at that node: 1000 (blue), 858 (dark green), 770 (light green), 659 (red). The Figure is adapted from Forde
et al. 2014 [
15].
Figure 1.
Maximum likelihood phylogenetic comparison of ST131 strains EC958, JJ1886, NA114 (clade C) and SE15 (clade A), and 16 representative strains from other
E. coli phylogroups. The phylogenetic relationships were inferred with the use of 70,777 SNPs identified between the genomes of the 20
E. coli strains and 1000 bootstrap replicates. The major
E. coli phylogroups are coloured as follows; group B2-ST131: (red); group B2 non-ST131: APEC-01, S88, 536, UTI89, CFT073, ED1A (orange); group D: UMN026, IAI39 (yellow); group A: BW2952, MG1655, W3110, HS (green); group B1: SE11, IAI1 (aquamarine); group E: O157 EDL933, O157 Sakai (blue). Nodes are coloured according to bootstrap support for branching at that node: 1000 (blue), 858 (dark green), 770 (light green), 659 (red). The Figure is adapted from Forde
et al. 2014 [
15].
Our own detailed genomic analysis focused on the major defining features of the three ST131 clades [
19]. While sequence analysis did not reveal any significant association with geographic origin, the majority of the single nucleotide polymorphisms that defined each clade were strongly associated with recombination. In total, 137 regions were defined as recombinant within our ST131 strain set, with the majority of large recombinant regions located adjacent to insertion sites for prophages and mobile genetic elements. Other recombination regions within the ST131 strain set were also identified, some of which encompassed virulence genes including
fimH, the
fliC flagella major subunit gene, and genes involved in capsule and O antigen biosynthesis. One other notable recombination region encompassed the
fimB recombinase gene that contributes to the regulation of type 1 fimbriae expression. Most ST131 strains from clade C have a 1,895bp insertion element within the
fimB gene (
fimB::ISEc55), suggesting they may possess an altered type 1 fimbriae expression profile. Indeed, the
fimB::ISEc55 insertion has been associated with a slower “off”-to-“on” type 1 fimbriae switching phenotype in ST131 [
20,
21]. We are currently investing the impact of this insertion on ST131 virulence.