ESBL Escherichia coli Isolates Have Enhanced Gut Colonization Capacity Compared to Non-ESBL Strains in Neonatal Mice

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli can cause invasive infections in infants and immunocompromised children with high associated morbidity and mortality. The gut is a major reservoir of these strains in the community. Current dogma dictates that antimicrobial resistance is associated with a fitness cost. However, recent data show that some contemporary ESBL E. coli strains may be more "fit" compared to nonresistant E. coli strains. Here, we use whole-genome sequencing to first characterize 15 ESBL E. coli strains isolated from infants in a Pakistani community, a clinical extraintestinal pathogenic ESBL E. coli ST131 strain, and a non-ESBL commensal E. coli strain, and then use a novel animal model of early life gut colonization to assess the ability of these strains to colonize the infant mouse gut. We determined that CTX-M-15 was present in all the ESBL strains, as well as additional beta-lactamases and genes conferring resistance to multiple antibiotic classes. In the animal model, 11/16 ESBL E. coli strains had significantly higher burden of colonization at week four of life compared to commensal strains, even in the absence of selective antibiotic pressure, suggesting that these strains may have enhanced fitness despite being highly antimicrobial resistant. IMPORTANCE Antimicrobial resistance is a global public health emergency. Infants, especially preterm infants and those in the neonatal intensive care unit, immunocompromised hosts, and those with chronic illnesses are at highest risk of adverse outcomes from invasive infections with antimicrobial-resistant strains. It has long been thought that resistance is associated with a fitness cost, i.e., antimicrobial-resistant strains are not able to colonize the gut as well as nonresistant strains, and that antibiotic exposure is a key risk factor for persistent colonization with resistant strains. Here, we use a novel infant mouse model to add to the growing body of literature that some highly-resistant contemporary Escherichia coli strains can persist in the gut with a significant burden of colonization despite absence of antibiotic exposure.