Multidrug-resistant E. coli encoding high genetic diversity in carbohydrate metabolism genes displace commensal E. coli from the intestinal tract

Abstract

Extra-intestinal pathogenic Escherichia coli (ExPEC) can cause a variety of infections outside of the intestine and are a major causative agent of urinary tract infections. Treatment of these infections is increasingly frustrated by antimicrobial resistance (AMR) diminishing the number of effective therapies available to clinicians. Incidence of multidrug resistance (MDR) is not uniform across the phylogenetic spectrum of E. coli. Instead, AMR is concentrated in select lineages, such as ST131, which are MDR pandemic clones that have spread AMR globally. Using a gnotobiotic mouse model, we demonstrate that an MDR E. coli ST131 is capable of out-competing and displacing non-MDR E. coli from the gut in vivo. This is achieved in the absence of antibiotic treatment mediating a selective advantage. In mice colonised with non-MDR E. coli strains, challenge with MDR E. coli either by oral gavage or co-housing with MDR E. coli colonised mice results in displacement and dominant intestinal colonisation by MDR E. coli ST131. To investigate the genetic basis of this superior gut colonisation ability by MDR E. coli, we assayed the metabolic capabilities of our strains using a Biolog phenotypic microarray revealing altered carbon metabolism. Functional pangenomic analysis of 19,571 E. coli genomes revealed that carriage of AMR genes is associated with increased diversity in carbohydrate metabolism genes. The data presented here demonstrate that independent of antibiotic selective pressures, MDR E. coli display a competitive advantage to colonise the mammalian gut and points to a vital role of metabolism in the evolution and success of MDR lineages of E. coli via carriage and spread.

Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan

“…However, our data further suggest that in the absence of recent antibiotic use or visit to a clinic, ST131 and ST69 are less competitive colonisers (in Punjab, Pakistan) than other lineages, as shown by their significantly higher frequencies in the outpatient follow-up samples. This finding contradicts the recent results from a gnotobiotic mouse model related to a superior MDR ST131 colonisation ability compared with ST73 as a resident strain 24 . Since the competition may be further influenced by nutrient availability and other factors of the wider host microbiota, further research is critically needed to generate a mechanistic understanding about the interplay of intrinsic and ecological factors determining the relative successes of the top lineages in a host population.…”

Antibiotic resistance alters the ability ofPseudomonas aeruginosato invade the respiratory microbiome

“…Interestingly, recent work has demonstrated how the ability of multi-drug resistant Escherichia coli lineages to displace commensal E. coli in the gut microbiome can be facilitated by encoding a high genetic diversity of carbohydrate metabolism genes, which can help provide a competitive advantage to invade in these environments (51).…”

“…Under this model, the growth of S. lugdunensis restricts P. aeruginosa indirectly via the consumption of nutrients needed for P. aeruginosa growth in this environment. Interestingly, recent work has demonstrated how the ability of multi-drug resistant Escherichia coli lineages to displace commensal E. coli in the gut microbiome can be facilitated by encoding a high genetic diversity of carbohydrate metabolism genes, which can help provide a competitive advantage to invade in these environments ( 51 ).…”

A Point Mutation in Cassette Relieves the Repression Regulation of CcpA Resulting in an Increase in the Degradation of 2,3-Butanediol in Lactococcus lactis

“…Tsigkrimani et al [29] successfully identified lactic acid bacteria in ripened Feta and Kefalograviera cheeses by using Gen III plates combined with other molecular techniques. In another study, Connor et al [36] tested for differences in carbon sources among three bacterial strains using PM1 assay plates. They detected significant differences in 34 carbon sources and identified multiple genes related to carbon metabolism.…”