NEW YORK (GenomeWeb) – The emergence of multidrug-resistant Escherichia coli populations appears to involve an evolutionary strategy that introduces new capabilities to the clones in question without giving the new clones full rein to take over a given host or environmental niche, new research suggests.
"Earlier research has shown that while ST131 emerged and rapidly spread in the late 1990s, it caused no more than 20 percent of clinical cases of E. coli once it had emerged on the scene," first author Alan McNally, a microbiology and infection researcher at the University of Birmingham, said in a statement. "Our research has shown this is because of a type of evolutionary selection called negative frequency dependency selection (NFDS)."
As they reported online today in mBio, McNally and colleagues from the UK, Norway, and Finland used artificial intelligence methods to profile whole-genome sequences for more than 850 drug-resistant E. coli isolates, focusing on a pathogenic clone called ST131 that can cause extra-intestinal pathogenic E. coli (ExEPC) infections such as bloodstream or urinary tract infections.
Based on the population genomic and antibiotic resistance gene patterns present in these isolates, the investigators suggested that E. coli ST131 follows a NFDS model of evolution that impacts accessory genes in the E. coli pan-genome, with clades expanding into new ecological niches without wiping out their competitors or reaching fixation in the population.
"Further studies are required to fully determine the extent to which niche separation and NFDS are either separate or linked processes," senior and co-corresponding author Jukka Corander, an infection genomics and biostatistics researcher affiliated with the Wellcome Sanger Institute, University of Norway, and University of Helsinki, and his co-authors wrote.
They added that "[u]nderstanding the processes that govern the epidemiological dynamics of dominant E. coli lineages, and those of similar pathogens causing bloodstream infections, is critical for addressing the public health threat of antibiotic resistance."
The researchers started with nearly 1,100 E. coli isolates from the British Society for Antimicrobial Chemotherapy that were collected from 2001 to 2011, identifying 862 ST131 representatives from that collection and from other prior studies that had available whole-genome sequence data.
Based on their analyses of the core and accessory genomes in isolates from the ST131 lineage, together with population frequency patterns and information on phylogenetic relationships between the E. coli clades, the authors proposed a model whereby E. coli "population structure and dynamics are shaped by NFDS acting on genomic islands."
In particular, the team saw extensive variation and signs of selection affecting genes that help E. coli ST131 bacteria colonize the gut, including genes that make it possible for the bugs to perform anaerobic metabolism — metabolic processes that occur in environments with little or no oxygen.
When the researchers assessed pan-genome data for hundreds of E. coli isolates from the ST73 or ST95 lineages — which can be involved in ExEPC infections, but typically do not contain multi-drug resistance plasmids or genes identified in the ST131 lineage — they saw more limited variation in genes from anaerobic metabolism pathways. Instead, those isolates tended to have more diverse virulence genes.
"Different resource strategies can facilitate co-existence between competing strains, such as those co-colonizing a host, resulting in frequency-dependent selection," the authors wrote, explaining that "diversification of metabolic loci could represent the adaptive radiation of particular traits within a successful genetic background."
Members of the team reportedly plan to continue analyzing E. coli isolates from other parts of the world, particularly Asia, and in settings outside of the human gut.