Abstract
Countering the rise of antibiotic resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g. via resource competition), but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three different human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonization by focal E. coli, they also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found highly effective resistance plasmids in resident microbial communities. We identified genetic constraints (lack of transfer genes) that can explain why our focal strain failed to acquire some of these plasmids, and for other plasmids further experiments revealed physical constraints on conjugative transfer. This suggests interactions with resident microbiota can inhibit antibiotic resistance evolution of individual species, and the potential for this to be counterbalanced by horizontal gene transfer depends on in situ transfer dynamics.