Insights into the acquisition of the pks island and production of colibactin in the Escherichia coli population

Abstract

The pks island codes for the enzymes necessary for synthesis of the genotoxin colibactin, which contributes to the virulence of Escherichia coli strains and is suspected of promoting colorectal cancer. From a collection of 785 human and bovine E. coli isolates, we identified 109 strains carrying a highly conserved pks island, mostly from phylogroup B2, but also from phylogroups A, B1 and D. Different scenarios of pks acquisition were deduced from whole genome sequence and phylogenetic analysis. In the main scenario, pks was introduced and stabilized into certain sequence types (STs) of the B2 phylogroup, such as ST73 and ST95, at the asnW tRNA locus located in the vicinity of the yersiniabactin-encoding High Pathogenicity Island (HPI). In a few B2 strains, pks inserted at the asnU or asnV tRNA loci close to the HPI and occasionally was located next to the remnant of an integrative and conjugative element. In a last scenario specific to B1/A strains, pks was acquired, independently of the HPI, at a non-tRNA locus. All the pks-positive strains except 18 produced colibactin. Sixteen strains contained mutations in clbB or clbD, or a fusion of clbJ and clbK and were no longer genotoxic but most of them still produced low amounts of potentially active metabolites associated with the pks island. One strain was fully metabolically inactive without pks alteration, but colibactin production was restored by overexpressing the ClbR regulator. In conclusion, the pks island is not restricted to human pathogenic B2 strains and is more widely distributed in the E. coli population, while preserving its functionality.

Correlation Between Antimicrobial Resistance, Virulence Determinants and Biofilm Formation Ability Among Extraintestinal Pathogenic Escherichia coli Strains Isolated in Catalonia, Spain

“…Colibactin may induce DNA damage in the host and has been correlated with colorectal cancer in humans (Wernke et al, 2020). Previous studies have confirmed the presence of pks-positive strains among ExPEC (Auvray et al, 2021). Interestingly, 75 of our isolates (19.9%) were colibactin-encoding strains, a higher percentage than this observed by Suresh et al (2018).…”

Two Polyketides Intertwined in Complex Regulation: Posttranscriptional CsrA-Mediated Control of Colibactin and Yersiniabactin Synthesis in Escherichia coli

“…Although HPI is not self-transferable, comparative genomic analyses and conjugation experiments indicated that joint horizontal transfer of the HPI can occur along with the pks island and another adjacent chromosomal island ( 59 ). In other colibactin-producing coliform enterobacteria, such as Klebsiella pneumoniae , Citrobacter koseri , and Klebsiella (formerly Enterobacter ) aerogenes , the colibactin and yersiniabactin determinants are colocalized within an integrative and conjugative element (ICE) ( 1 – 3 ), confirming that physical linkage of the colibactin and yersiniabactin islands is actively supported by joint acquisition or spread via horizontal gene transfer.…”

“…A variety of Escherichia coli strains belonging to the phylogenetic group B2, which comprises extraintestinal pathogenic E. coli (ExPEC) as well as commensal E. coli strains, have been identified to carry two potentially linked genomic islands, namely, the so-called “high pathogenicity island” (HPI) and the polyketide synthase ( pks ) island. Both islands are chromosomally located in close proximity, and the pks island always coexists with the HPI ( 1 – 3 ). Each island carries all necessary genes for a combined polyketide synthase (PKS) and nonribosomal peptide synthase (NRPS) biosynthesis machinery, producing either colibactin or yersiniabactin.…”

Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?

“…E. coli group B2 includes commensal strains and pathogenic strains that are responsible for extra-intestinal diseases, including urinary tract infections, sepsis, pneumonia, and neonatal meningitis. Among the strains of the B2 phylogroup, there are a large number of strains that possess in their genome the pks island that encodes the genotoxin colibactin [3,4]. These pks + strains of E. coli are frequently found in asymptomatic carriage in the digestive tract from the first days after birth [5,6].…”

“…The pks island encoding enzymes responsible for colibactin biosynthesis is mainly present in this group. The sequence of the pks island is highly conserved and pks-carrying (pks + ) strains are found overwhelmingly capable to produce colibactin [3]. The biosynthesis of colibactin has been summarized in two nice reviews [8,9].…”