Insights into the acquisition of the pks island and production of colibactin in the Escherichia coli population
Résumé
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.
Mots clés
sequence type
tRNA
transfer ribonucleic acid
VNTR
ST
Single nucleotide polymorphism
SNP
PK synthase
PKS
NRP synthetase
NRPKS
neighbour joining
NJ
most recent common ancestor
MRCA
colibactin
IS
Integrase
Int
interstrand cross-link
ICL
integrative and conjugative element
ICE
high pathogenicity island
HPI
horizontal gene transfer
HGT
extra-intestinal pathogenic E. coli
ExPEC
Direct repeats
DR
colony forming unit
CFU
clonal complex
CC
asparagine
pks. Abbreviations: asn
pks
pathogenicity island
genotoxin
genetic diversity
Escherichia coli
enterobacteria
insertion sequence
maximum likelihood
ML
variable number of tandem repeat
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