Sequencing a piece of history: complete genome sequence of the original Escherichia coli strain

Abstract

In 1885, Theodor Escherich first described the Bacillus coli commune, which was subsequently renamed Escherichia coli. We report the complete genome sequence of this original strain (NCTC 86). The 5 144 392 bp circular chromosome encodes the genes for 4805 proteins, which include antigens, virulence factors, antimicrobial-resistance factors and secretion systems, of a commensal organism from the pre-antibiotic era. It is located in the E. coli A subgroup and is closely related to E. coli K-12 MG1655. E. coli strain NCTC 86 and the non-pathogenic K-12, C, B and HS strains share a common backbone that is largely co-linear. The exception is a large 2 803 932 bp inversion that spans the replication terminus from gmhB to clpB. Comparison with E. coli K-12 reveals 41 regions of difference (577 351 bp) distributed across the chromosome. For example, and contrary to current dogma, E. coli NCTC 86 includes a nine gene sil locus that encodes a silver-resistance efflux pump acquired before the current widespread use of silver nanoparticles as an antibacterial agent, possibly resulting from the widespread use of silver utensils and currency in Germany in the 1800s. In summary, phylogenetic comparisons with other E. coli strains confirmed that the original strain isolated by Escherich is most closely related to the non-pathogenic commensal strains. It is more distant from the root than the pathogenic organisms E. coli 042 and O157 : H7; therefore, it is not an ancestral state for the species.

Keywords: Escherichia coli; Theodor Escherich; genome sequence.

Fig. 1.

Circular representation of the E. coli NCTC 86 chromosome. From the outside to inside, circle 1 shows the sizes in bp. Circle 2 marks the positions of RODs. Circles 3 and 4 show the positions of CDSs transcribed in a clockwise and anticlockwise direction. Circles 5 to 10 show the positions of E. coli NCTC 86 genes that have orthologues (by reciprocal fasta analysis) in other E. coli strains: K-12 MG1655 (red), E24377A (ETEC; yellow), 042 (ETEC; green), Sakai (0157 : H7; blue), IAI39 (Extraintestinal Pathogenic E. coli; pink), CFT073 (UPEC; orange). Circle 11 shows a plot of G+C content. Circle 12 shows a plot of G+C skew.

Fig. 2.

Global comparison between of the chromosomes of E. coli NCTC 86 and E. coli K-12 MG1655. The red bars between the DNA lines represent individual tblastx matches, with inverted matches coloured blue. Regions where inversion occurs have been expanded, with RNA genes in green, backbone flanking regions in purple, and either side of the inversion in blue and orange. The products arising from PCR amplification of genomic DNA with primers corresponding to gmhB (primer 1) and dkgB (primer 2) or kgtP (primer 3) were separated by agarose gel electrophoresis and are shown in insets; sizes (bp) are shown on the left of the gel images.

Fig. 3.

Phylogenetic relationships amongst sequenced E. coli genomes. The genomes of E. albertii and E. fergusonii are included as outgroup sequences. The tree was obtained by maximum likelihood analysis of a concatenated alignment of 2173 genes, using the general time reversible (GTR/REV) model, with the CAT approximation of rate heterogeneity as implemented in RAxML version 8.1.3. The numbers on individual branches indicate the percentage support from 100 non-parametric bootstrap replicates, performed using the rapid algorithm implemented in RAxML. The branch length indicates the number of substitutions per site. The major E. coli phylogenetic groups are indicated.

Fig. 4.

Comparison of the genetic content of E. coli NCTC 86 with other genome-sequenced E. coli. The three strains belong to the same phylogenetic group (group A) and share 3640 common genes. E. coli HS and NCTC 86 share 104 genes that are not present in E. coli K-12. Similarly, E. coli K-12 has 272 genes in common with E. coli NCTC 86 that are absent in E. coli HS. E. coli HS and K-12 share 57 genes that are absent from E. coli NCTC 86. All strains possess a complement of unique genes not present in the other strains; there are 789 genes present in E. coli NCTC 86 not present in E. coli K-12 or E. coli HS, 719 genes present in E. coli HS not present in E. coli K-12 and NCTC 86, and 408 genes in E. coli K-12 not found in E coli HS or NCTC 86.

Fig. 5.

Genetic architecture and distribution of the CU systems of E. coli NCTC 86. Phylogenetic distribution of the fimbrial loci amongst pathogenic and non-pathogenic lineages of E. coli. The loci encoding the fimbrial systems demonstrate a differential distribution amongst the E. coli phylogeny. The branch lengths indicate the number of substitutions per site.