Prevalence and Genetic Diversity of E. coli CC38 from Danish Human Cases
Recent research has shed light on the prevalence and genetic makeup of E. coli CC38 among Danish patients, based on an extensive analysis of 242 isolates derived from 240 individuals. Of these isolates, an overwhelming majority—219—were identified as ST38, accounting for 91% of the total. The remaining isolates included five categorized as ST3666. Intriguingly, all isolates were traced to phylogroup D, and they exhibited a notable variety of fimH types, with fimH5 being the most prevalent (n=136, or 56%), followed by fimH0 (n=45, 19%), fimH65 (n=21, 9%), fimH54 (n=16, 7%), and fimH116 (n=11, 5%).
Genomic analyses revealed the presence of 16 different resistance genes among the isolates, including extended-spectrum beta-lactamases (ESBL), plasmid-mediated AmpC (pAmpC), and carbapenemase-encoding genes. The most commonly detected among these was blaCTX-M-14 (n=101, 42%), followed by blaCTX-M-15 (n=62, 26%), blaOXA-244 (n=45, 19%), and blaOXA-48 (n=34, 14%). A significant portion of the genomes (n=165, or 68%) harbored resistance genes linked to a single class of beta-lactamase, predominantly ESBLs (n=142, 59%). Interestingly, 77 genomes (32%) showcased combinations of two resistance classes, with the pairing of ESBL and carbapenemase being the most frequently observed.
On February 18, 2020, the European Centre for Disease Prevention and Control (ECDC) released a Rapid Risk Assessment regarding the surge of E. coli strains producing the carbapenemase OXA-244, updating it later on July 20, 2021. During the period from January 2016 to August 2019, Denmark recorded 23 cases of OXA-244-producing E. coli, including 13 ST38 isolates. Between September 2019 and December 2022, an additional 31 isolates of this strain were detected, with 35 of the OXA-244 producers also carrying other ESBL genes, and six possessing the pAmpC gene blaCMY-2.
Clonal Relatedness and Outbreaks of E. coli CC38
To better understand the clonal relationships and potential outbreak scenarios related to E. coli CC38 in Denmark, researchers undertook a meticulous genomic analysis. This investigation revealed a staggering 48,050 single nucleotide polymorphisms (SNPs) among the 242 human genomes, covering approximately 69% of the reference chromosome from the E. coli strain 190693. After filtering out recombinant regions, 5,159 phylogenetically informative SNPs remained, leading to the identification of 14 plausible clonal clusters and 10 potential outbreak clusters.
The research highlighted two significant findings: the carbapenemase blaOXA-244 gene was identified in two potential outbreak clusters, while blaOXA-48 was detected in five. Notably, only one case revealed a direct epidemiological link involving three patients, who had overlapping hospital stays. Their E. coli isolates exhibited minimal genetic divergence, differing by less than one SNP. However, for other clusters, establishing direct epidemiological links proved elusive.
Additionally, a noteworthy case of departmental accumulation surfaced, where five patients were connected through the same hospital unit over time, although no formal links could be established. Within the seven potential outbreak clusters containing carbapenemase-producing isolates, travel history was available for only three, underscoring the challenges in tracing the origin of these isolates.
Zoonotic Transmission: The Foodborne Link
To further investigate the potential foodborne transmission pathways of CC38 in Denmark, a comparative analysis was conducted between the human and veterinary E. coli collections. This comparison revealed a total of 51,459 SNPs among approximately 68% of the reference chromosome. However, direct genomic links between the two collections were absent, despite the identification of two distinct phylogenetic groups—DK-Group I, predominantly made up of human isolates, and DK-Group II, containing isolates from poultry, livestock, and other food sources.
In estimating the zoonotic contributions, the research predicted source-associated mobile genetic elements from both human and poultry isolates. The results indicated that while DK-Group II isolates were largely of poultry origin, DK-Group I was predominantly human-associated. Interestingly, some subgroups within DK-Group I showed mixed predictions, suggesting potential cross-species transmission.
Global Phylogenetic Reconstruction and Cluster Analysis of E. coli CC38
Expanding the scope of the research, 2,638 genomes meeting inclusion criteria were analyzed, spanning isolates collected from 1979 to 2022. Among these, a significant number (n=1,682, or 64%) were from human cases, with the remainder derived from various sources including poultry, wildlife, and water bodies. Notably, contributions from Europe were the highest (n=950, or 36%), closely followed by North America.
The investigation of genetic relationships among these global isolates uncovered two primary clusters: Cluster I, linked to poultry, and Cluster II, predominantly associated with human cases. Detailed examination of these clusters revealed varying antimicrobial resistance profiles. Cluster I was notable for moderate resistance primarily via ESBL genes and featured a high ratio of hybrid ExPEC-UPEC strains. In contrast, Cluster II displayed a broader host range and significantly higher resistance and virulence factors, with many isolates lacking the fimH gene altogether.
The findings from this extensive research not only underscore the complexities of E. coli CC38 strains circulating in Denmark but also highlight the intricate web of connections between health, environment, and food sources. As we advance, understanding these relationships will be crucial in curbing the spread of antibiotic-resistant strains and enhancing public health strategies.
