Comparative genomics and phenotypic studies to determine site-specificity of Escherichia coli in the lower gastrointestinal tract of humans

ABSTRACT

Escherichia coli (E. coli) is an important commensal in the human gut; however, it is unknown whether strains show site-specificity in the lower gut. To investigate this, we assessed genotypic and phenotypic differences in 37 clone pairs (two strains with very similar multiple locus variable-number-tandem-repeat analysis [MLVA] profiles) of E. coli isolated from mucosal biopsies of two different gut locations (terminal ileum and rectum). The clone pairs varied at the genomic level; single nucleotide polymorphisms (SNPs) were common, multiple nucleotide polymorphisms (MNPs) were observed but less common, and few indels (insertions and deletions) were detected. The variation was higher in clone pairs that are associated with non-human-associated sequence types (ST) compared to human-associated STs, such as ST95, ST131, and ST73. No gene(s) with non-synonymous mutations were found to be commonly associated with either the terminal ileum or the rectal strains. At the phenotypic level, we identified the metabolic signatures for some STs. Rectum strains of some STs showed consistently higher metabolic activity with particular carbon sources. Clone pairs belonging to specific STs showed distinct growth patterns under different pH conditions. Overall, this study showed that E. coli may exhibit genomic and phenotypic variability at different locations in the gut. Although genomics did not reveal significant information suggesting the site-specificity of strains, some phenotypic studies have suggested that strains may display site-specificity in the lower gut. These results provide insights into the nature and adaptation of E. coli in the lower gut of humans. To the best of our knowledge, no study has investigated or demonstrated the site-specificity of commensal E. coli in the human gut.

KEYWORDS:

• E. coli
• site-specificity
• human gut
• terminal ileum
• rectum
• adaptation

Acknowledgments

We thank the patients who provided specimens for this study. We are grateful to the doctors, nurses, and staff of the Gastroenterology and Hepatology Unit of Canberra Hospital, ACT, Australia.

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Author contribution

RB collected specimens, designed, and conducted the experiments, performed formal analysis, interpreted the results, and wrote the original draft; PP conceptualized the study, acquired funding, and reviewed the manuscript; DMG conceptualized and designed the study, interpreted the results, administered the project, and reviewed the manuscript; COB conceptualized and designed the study, interpreted the results, acquired funding, administered the project, and reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The genome sequences of Escherichia coli strains used in this study were deposited and are available in EnteroBase (https://enterobase.warwick.ac.uk/).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2223332

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Canberra Hospital Private Practice Trust Fund.