E. coli bacteraemia, genomic epidemiology, multi-drug resistant, whole genome sequencing, ST131, geographic analysis, Phylogenomic analysis, pathogenic Gram-negative bacilli
Introduction:
The increasing resistance to third-generation cephalosporins (3GCs) is detrimental to public health, as these antimicrobials are prescribed as empirical therapies for systemic infections caused by Gram-negative bacteria. Uropathogenic Escherichia coli sequence type (ST)131 is a globally disseminated, multidrug-resistant lineage associated with resistance to 3GCs in urinary tract infections (UTIs) and bacteraemia.
Methods:
This work combined whole-genome sequencing (WGS) and epidemiology to investigate ST131 associated with bacteraemia in Wales between 2013-2014. To investigate spatial clusters and lineage diversity, we contextualised 142 genomes collected from twenty hospitals, representing six university health boards (UHB), against a global ST131 population (n=181).
Results:
All three major ST131 clades are represented across Wales, with clade C/H30 predominant (n=102/142, 71.8%). Consistent with global findings, 63.7% (n=65/102) and 59.8% (n=61/102) of clade C/H30 Welsh strains contained genes from the blaCTX-M-1 group and blaOXA-1, respectively, which confer resistance to 3GCs. Most Welsh clade C/H30 strains belonged to clade C2/H30Rx (n=88/151, 58.3%) meanwhile Welsh strains within clade C1/H30R are less common (n=14/67, 20.9%). We identified a sub-lineage within the C2/H30Rx clade unique to Wales (GB-WLS.C2/H30Rx) and is defined by six SNPs, including a missense variant in febE (ferric enterobactin transport protein) and fryC (Fructose-like permease IIC component), and the loss of the capsular biosynthesis genes encoding the K5 antigen. Bayesian analysis predicted that the common ancestor (CA) to GB-WLS.C2/H30Rx diverged from a shared Canadian strain between 1998-1999. Further, a GB-WLS.C2/H30Rx descendent entered North Wales circa 2002, persisted, and caused a cluster of cases with a maximum pairwise distance of 30 SNPs where the CA emerged circa 2009.
Conclusion:
The limited genomic diversity amongst geographically-restricted strains forming the GB-WLS.C2/H30Rx cluster likely represents an environmentally mediated transmission of a single strain within the community of North Wales. This investigation emphasises the value of genomic epidemiology, allowing for the detection of putative transmission clusters and local clonal expansion events, enabling early targeted public health interventions.