Multi-drug resistantE. colidisplace commensalE. colifrom the intestinal tract, a trait associated with elevated levels of genetic diversity in carbohydrate metabolism genes

Abstract

AbstractExtra-intestinal pathogenicE. 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 multi-drug resistance (MDR) is not uniform across the phylogenetic spectrum ofE. 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 MDRE. coliST131 is capable out-competing and displacing non-MDRE. colifrom the gutin vivo. This is achieved in the absence of antibiotic treatment mediating a selective advantage. In mice colonised with non-MDRE. colistrains, challenge with MDRE. colieither by oral gavage or co-housing with MDRE. colicolonized mice results in displacement and dominant intestinal colonization by MDRE. coliST131. To investigate the genetic basis of this superior gut colonization ability by MDRE. coli, we used a functional pangenomic analysis of 19,571E. coligenomes revealing 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, MDRE. colidisplay a competitive advantage to colonise the mammalian gut and points to a vital role of metabolism in the evolution and success of MDR lineages ofE. colivia carriage and spread.