The origin, evolution and population structure of 4,071 global Escherichia coli ST131 genomes

Thursday 17 October 2019, 1.00PM

Speaker(s): Tim Downing, School of Biotechnology, Dublin City University, Dublin, Ireland

Background: Advances in the genomic resolution of large bacterial collections facilitates the study of specific evolutionary events across core and accessory genomes. The widespread use of beta-lactam antibiotics drives the adaptation of extended-spectrum beta-lactamase (ESBL) genes in many pathogenic bacteria. These ESBL genes often transferred to new chromosomal or plasmid locations by mobile genetic elements (MGEs), during which the ESBL genes are often amplified, truncated or mutated. Plasmid transfer between bacteria and subsequent recombination at ESBL genes and MGEs further extend the complexity of rearrangement at variable genomics regions. Here, we use Escherichia coli ST131 as a paradigm for genomic bacterial epidemiology because it is a major cause of infection with extensive antimicrobial resistance (AMR) driven by its dynamic accessory genome.

Methods: By extracting all available high-quality global ST131 Illumina HiSeq read libraries, we automated quality-control, genome de novo assembly, DNA read mapping, plasmid reconstruction and ESBL gene screening in the largest ST131 sample collection examined thus far. We reconstructed the genealogical histories of these 4,071 genomes to infer their population structure and recombination patterns. We used long Nanopore and PacBio reads, published reference genomes and efficient k-merbased methods to contextualise the core and accessory genome diversity observed to pinpoint the key emerging ST131 subclades.

Results: The three main C ST131 subclades have co-circulated globally at relatively stable frequencies over time, suggesting their relative frequencies stabilise after their origin and initial rapid spread. This contrasted with their ESBL genes, which had stronger patterns across time, geography and subclade, and were located at distinct locations across the chromosomes and plasmids between isolates. Within the three C subclades, the core and accessory genome diversity levels were not correlated due to plasmid and MGE activity, unlike patterns between the three main clades, A, B and C.

Conclusion: This population genomic study highlights the dynamic nature of the accessory genomes in ST131, suggesting that surveillance should anticipate genetically variable outbreaks with broader antibiotic resistance levels. Our findings emphasise the potential of evolutionary pangenomics to improve our understanding of AMR gene transfer, adaptation and transmission to discover accessory genome changes linked to novel subtypes.

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Location: Dianna Bowles Lecture Theatre B/K/018