Loss of type VI secretion systems in multi-drug resistant Escherichia coli clones

The repeated emergence of multi-drug resistant (MDR) Escherichia coli clones is a threat to public health globally. In recent work, drug resistant E. coli were shown to be capable of displacing commensal E. coli in the human gut. Given the rapid colonisation observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug resistant E. coli clones. We employed large scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20,000 genomes representing the full phylogenetic diversity of E. coli. This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterised the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones. Data SummaryThe genome sequence data generated in this study is publicly available from NCBI under BioProject PRJNA943186, alongside a complete assembly in GenBank under accessions CP120633-CP120634. All other sequence data used in this paper has been taken from ENA with the appropriate accession numbers listed within the methods section. The E. coli genome data sets used in this work are from a previous publication, the details of which can be found in the corresponding supplementary data files 10.6084/m9.figshare.21360108 [1]. Impact StatementEscherichia coli is a globally significant pathogen that causes the majority of urinary tract infections. Treatment of these infections is exacerbated by increasing levels of drug resistance. Pandemic multi-drug resistant (MDR) clones, such as ST131-C2/H30Rx, contribute significantly to global disease burden. MDR E. coli clones are able to colonise the human gut and displace the resident commensal E. coli. It is important to understand how this process occurs to better understand why these pathogens are so successful. Type VI secretion systems may be one of the antagonistic systems employed by E. coli in this process. Our findings provide the first detailed characterisation of the T6SS loci in ST410 and ST131 and shed light on events in the evolutionary pathways of the prominent MDR pathogens ST410-B4/H42RxC and ST131-C2/H30Rx.