Within‐host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract

Abstract

When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E. coli diversity in a host, a collection of multiple E. coli isolates recovered from each of 67 patients undergoing colonoscopies was used. Whole genome sequence data were available for one example of every REP-fingerprint type identified in a patient. Sequence type (ST) and single-nucleotide polymorphism (SNP) analyses revealed that 83% of strains observed in the host population were a consequence of immigration/establishment events. Restricting the analysis to hosts harboring two or more strains belonging to the same phylogroup revealed that in about half of these cases, the presence of a second strain belonging to the same phylogroup was the consequence of an independent immigration/establishment event. Thus, the results of this study show that despite hosts being exposed to a diversity of E. coli via their food, factors related to the host also determine what E. coli strains succeed in establishing.

Genomic diversity of Escherichia coli isolates from healthy children in rural Gambia

“…We found that within-host evolution plays a minor role in the generation of diversity, in line with Dixit et al (20), who reported that 83% of diversity originates from immigration events, and with epidemiological data suggesting that the recurrent immigration events account for the high faecal diversity of E. coli in the tropics (47). Co-colonising variants belonging to the same ST tended to share an identical virulence, AMR and plasmid profile, signalling similarities in their accessory gene content.…”

“…Following Dixit et al (20), we sequenced a random selection of isolates twice, using DNA obtained from independent cultures, to help in the determination of clones and the analysis of 6 within-host variants (Supplementary File 5). Bioinformatic analyses of the genome sequences were carried out on the Cloud Infrastructure for Microbial Bioinformatics (CLIMB) platform (35).…”

“…We computed pairwise single nucleotide polymorphism (SNP) distances between genomes from the core-genome alignment using snp-dists v0.6 (https://github.com/tseemann/snp-dists). For the duplicate sequence reads of the same strains, we used SPAdes v3.13.2 (40) to assemble each set of reads and map the raw sequences from one sequencing run to the assembly of the other run and vice versa, as described previously (20). SNPs were detected using the CSIPhylogeny tool (https://cge.cbs.dtu.dk/services/CSIPhylogeny/) and compared between the two steps, counting only those SNPs that were detected in both sets of reads as accurate.…”

“…Although clinical microbiology typically relies on single-colony picks (which has the potential to underestimate species diversity and transmission events), within-host diversity of E. coli in the gut is crucial to our understanding of inter-strain competition and co-operation and also for accurate diagnosis and epidemiological analyses. Pioneering efforts using serotyping and molecular typing have shown that normal individuals typically harbour more than one strain of E. coli (20)(21)(22), with one individual carrying 24 distinct clones (22)(23)(24).…”

“…Strains originating from serial immigration events are likely to differ by hundreds or thousands of single-nucleotide polymorphisms (SNPs). Alternatively, within-host evolution can generate clouds of intra-clonal diversity, where genotypes differ by just a handful of SNPs (20).…”