Abstract
Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 deaths annually, with the highest rates of burden, ca 75 million cases per year, amongst children under 5 years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide. We used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. We confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades, suggesting that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.
Highlights
Diarrheal pathogens are a leading cause of morbidity and mortality globally (WHO 2017), with enterotoxigenic Escherichia coli (ETEC) accounting for a large proportion of the diarrhoea cases in resource-poor c ountries[1]
Enterotoxigenic Escherichia coli (ETEC) bacteria adhere to the small intestine through fimbrial, fibrillar or afimbrial outer membrane-structures called colonisation factors (CF)
Overall the results show that ETEC plasmids are specific to lineages circulating worldwide and conserved over time (Fig. 1, Figures S2–S3, and Figures S4–S11 for more extensive plasmid annotation)
Summary
Diarrheal pathogens are a leading cause of morbidity and mortality globally (WHO 2017), with enterotoxigenic Escherichia coli (ETEC) accounting for a large proportion of the diarrhoea cases in resource-poor c ountries[1]. The most vulnerable group is children under five years, but ETEC can cause disease in adults and is the principal cause of diarrhoea in travellers. There is strong evidence to support that an ETEC vaccine is of key importance to prevent children and adults from developing ETEC disease[3]. The bacteria proliferate and secrete heat-labile toxin (LT) and/or heat-stable toxins, (STh or STp) causing diarrhoea and often vomiting causing the further spread of the bacteria in the e nvironment[7]. 27 different CFs with human tropism have been described, and individual ETEC strains usually express 1–3 different. Human-associated ETEC strains express one of the 28 different LT-I variants (LTh-1 and LTh-2 are the most common variants)[15] alone or together with one of the genetically distinct types of STa; STh and STp16,17
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