Comparative genome analysis identifies few traits unique to the Escherichia coli ST131 H30Rx clade and extensive mosaicism at the capsule locus

Abstract

BackgroundE.coli ST131 is a globally disseminated clone of multi-drug resistant E. coli responsible for that vast majority of global extra-intestinal E. coli infections. Recent global genomic epidemiological studies have highlighted the highly clonal nature of this group of bacteria, however there appears to be inconsistency in some phenotypes associated with the clone, in particular capsule types as determined by K-antigen testing both biochemically and by PCR.ResultsWe performed improved quality assemblies on ten ST131 genomes previously sequenced by our group and compared them to a new reference genome sequence JJ1886 to identify the capsule loci across the drug-resistant clone H30Rx. Our data shows considerable genetic diversity within the capsule locus of H30Rx clone strains which is mirrored by classical K antigen testing. The varying capsule locus types appear to be randomly distributed across the H30Rx phylogeny suggesting multiple recombination events at this locus, but that this capsule heterogeneity has little to no effect on virulence associated phenotypes in vitro.ConclusionsOur data provides a framework for determining the capsular genetics of E. coli ST131 and further beyond to ExPEC strains, and highlights how capsular mosaicism may be an important strategy in becoming a successful globally disseminated human pathogen.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-830) contains supplementary material, which is available to authorized users.

Diversity and evolution of surface polysaccharide synthesis loci in Enterobacteriales

“…These results point to important differences in the evolutionary dynamics of SP locus sharing between different species, and are consistent with previous studies of antigen variation in some individual species. For example, frequent exchange of K and O antigen loci has been observed within E. coli lineages [53,54], whereas O antigen (cps) loci are maintained in S. enterica lineages to the point that lineage typing has been proposed as a substitute for serotyping [44]. In K. pneumoniae, the cps K locus is a hotspot for recombination in many lineages, but in others is conserved for long evolutionary periods [51].…”

Biochemical Characterization of Bifunctional 3-Deoxy-β-d-manno-oct-2-ulosonic Acid (β-Kdo) Transferase KpsC from Escherichia coli Involved in Capsule Biosynthesis

“…In E. coli, they are found in extra-intestinal isolates, including the globally disseminated multidrug-resistant ST131 group responsible for the majority of extra-intestinal infections by this species (9). The same assembly pathway is also used by opportunistic human pathogens (e.g.…”

Signatures of negative frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli

“…However, as these traits become more common as ST131 expands, representatives of this lineage will more commonly encounter one another, therefore necessitating further diversification for different clade C representatives to sustain their advantage over competitors. Similarly, the capsule locus diversification previously observed within clade C, resulting in the capsule synthesis locus corresponding to a ‘hotspot’ of recombination 35 , could result from NFDS of variable antigens 54 , with the host immune system selecting for a diversity of capsule structures as the dominant type becomes more common following ST131’s emergence 16 .…”

“…This might enable the clade to avoid the limitations of any loci that NFDS would suppress to low frequencies. Hence the underlying genotype of ST131 appears to represent a highly-fit genotype that has subsequently diversified into both antibiotic-sensitive (clade B) and resistant (clade C) forms, expressing one of multiple capsules 35 . Therefore a comprehensive genomic dataset encompassing all known ST131 genome sequences was created to understand the unique characteristics of the ST131 lineage, with particular focus on the successful clades B and C.…”

“…The importance of iron acquisition can also explain many of the MDR efflux allele variants seen in this data set, with half occurring in the acrD gene which has been experimentally shown to play a role in iron acquisition in E. coli 45 . We identified multiple alleles of genes in the type 1 fimbriae operon and in genes in the P pilus operon which are classical virulence determinants in UTI 46 , and multiple genes involved in capsule biosynthesis, which we have previously reported as being a hotspot for recombination in E. coli ST131 13,35 . We also identified multiple alleles of genes involved in controlling incomplete septation and filamentous growth, which is a crucial process in the formation of the filamentous intracellular bacterial communities (IBCs) which are thought to be fundamental in the ability of ExPEC to survive inside bladder epithelial cells and cause UTI 47 .…”