Evolution of the murine gut resistome following broad-spectrum antibiotic treatment

Abstract

The emergence and spread of antimicrobial resistance (AMR) represent an ever-growing healthcare challenge worldwide. Nevertheless, the mechanisms and timescales shaping this resistome remain elusive. Using an antibiotic cocktail administered to a murine model along with a longitudinal sampling strategy, we identify the mechanisms by which gut commensals acquire antimicrobial resistance genes (ARGs) after a single antibiotic course. While most of the resident bacterial populations are depleted due to the treatment, Akkermansia muciniphila and members of the Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae families acquire resistance and remain recalcitrant. We identify specific genes conferring resistance against the antibiotics in the corresponding metagenome-assembled genomes (MAGs) and trace their origins within each genome. Here we show that, while mobile genetic elements (MGEs), including bacteriophages and plasmids, contribute to the spread of ARGs, integrons represent key factors mediating AMR in the antibiotic-treated mice. Our findings suggest that a single course of antibiotics alone may act as the selective sweep driving ARG acquisition and incidence in gut commensals over a single mammalian lifespan.

Postnatal 14D is the Key Window for Mice Intestinal Development‐ An Insight from Age‐Dependent Antibiotic‐Mediated Gut Microbial Dysbiosis Study

“…So we can hypothesize that only one phylum Proteobacteria outnumbered and increased the total microbiota abundance in the P28D AVNM group, which could result from the emergence of a resistant population of Enterobacteriaceae family under the Proteobacteria phylum. [64] We also observed the high relative abundance of Klebsiella and Enterobacter in the genus level (Figure 3F), which correspond to the Enterobacteriaceae family from our data. Despite a bloom of Proteobacteria in the AVNM-exposed neonate gut, which is linked with a higher risk of disease, [65] a hostdependent mechanism [66] could mitigate the effect of perturbed microbiota during chronic dysbiosis and bring it back to normalcy.…”

Characterization of antibiotic-resistance traits in Akkermansia muciniphila strains of human origin

“…According to Guo et al 15 A. muciniphila acquired genes during its evolution, from a wide range of taxa associated with human intestinal habitat, through horizontal gene transfer. Furthermore, de Nies et al 16 highlighted that A. muciniphila has a plastic genome, that is particularly prone to acquire ARGs under antibiotics selective pressure. In light of the above, we wanted also to screen the A. muciniphila strains for the presence of mobile genetic elements (MGEs), possibly involved in the ARGs transfer.…”

“…The gut microbiome, the main source of these health-promoting microbes, is considered a reservoir of ARGs and the anaerobic commensal species represent the main contributors to the human intestinal resistome 13 , 14 . Specifically, A. muciniphila is thought to be particularly plastic and prone to gaining antimicrobial resistance (AMR) 15 , 16 . In Europe, information on AMR for bacteria deliberately introduced into the food chain is of paramount importance to declaring a microorganism safe for human and animal consumption.…”

The Skin Microbiome: Current Landscape and Future Opportunities

“…In addition, AMR poses an urgent global healthcare challenge [ 318 ]; therefore, it is essential to develop non-antibiotic therapies to treat infection. It is now also appreciated that broad-spectrum antibiotics deplete the resident microbiota, contributing to the growth of AMR organisms [ 319 , 320 ]. Hence, emergent therapies must specifically target pathogens to ameliorate any impact on host commensals.…”