Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli strains

Abstract

Large-scale bacterial genome sequencing efforts to date have provided limited information on the most prevalent category of disease: sporadically acquired infections caused by common pathogenic bacteria. Here, we performed whole-genome sequencing and de novo assembly of 312 blood-or urine-derived isolates of extraintestinal pathogenic (ExPEC) Escherichia coli, a common agent of sepsis and community-acquired urinary tract infections, obtained during the course of routine clinical care at a single institution. We find that ExPEC E. coli are highly genomically heterogeneous, consistent with pangenome analyses encompassing the larger species. Investigation of differential virulence factor content and antibiotic resistance phenotypes reveals markedly different profiles among lineages and among strains infecting different body sites. We use high-resolution molecular epidemiology to explore the dynamics of infections at the level of individual patients, including identification of possible person-to-person transmission. Notably, a limited number of discrete lineages caused the majority of bloodstream infections, including one subclone (ST131-H30) responsible for 28% of bacteremic E. coli infections over a 3-yr period. We additionally use a microbial genome-wide-association study (GWAS) approach to identify individual genes responsible for antibiotic resistance, successfully recovering known genes but notably not identifying any novel factors. We anticipate that in the near future, whole-genome sequencing of microorganisms associated with clinical disease will become routine. Our study reveals what kind of information can be obtained from sequencing clinical isolates on a large scale, even well-characterized organisms such as E. coli, and provides insight into how this information might be utilized in a healthcare setting.

Extra-intestinal pathogenic Escherichia coli (ExPEC): Disease, carriage and clones

“…As the cost of WGS falls it is likely to be used increasingly for surveillance and routinely in clinical practice. However, for reasons relating to standardisation, the ST nomenclature derived from well-established MLST schemes seems likely to be retained, even if the PCR-based methodologies themselves are replaced and ST data are, in future, largely derived from whole genome analysis (14,27).…”

The importance of the “V”-Factor:Escherichia colibacteremia and sepsis

“…More robust examination of the genomic sequence of ExPEC strains was performed by Salipante et al 2015. 10 Using clinical isolates obtained from routine diagnostic culture of peripheral blood and or urine and focusing on more than 3 thousand genes determined no evidence of a phylogenomic division between infectious strains. This study also revealed that differences in VF content and antibiotic resistance phenotypes, which distinguish population level group of E. coli, do not persist when the overall population structure is taken into account.…”

Clonal distribution and associated characteristics of Escherichia coli clinical and surveillance isolates from a military medical center

“…Phylogroup B2 isolates were uniquely over-represented among the clinical isolates. Phylogroup A isolates (specifically ST10), although somewhat more common among surveillance than clinical isolates, were more common among clinical isolates than expected based on prior work (Salipante et al, 2015).…”

“…b Antimicrobial classes are listed first, followed by the corresponding individual agents that were tested. No resistance was detected to carbapenems (imipenem, meropenem (Salipante et al, 2015). ST10 was more prevalent among clinical isolates than expected, which could be due to a greater frequency of cutaneous carriage (Table 1).…”