Multi-layered ecological interactions determine growth of clinical antibiotic-resistant strains within human microbiomes.

The spread of antibiotic-resistant bacteria in the gut depends on their ability to establish within complex microbial communities. However, the role of various ecological factors in modulating this process, particularly in the absence of antibiotic selection, remains poorly understood. We hypothesize that different strains within the same species vary in their ability to colonize due to distinct interactions with resident microbiota. Using human gut-microbiome samples in replicated anaerobic microcosms with and without antibiotics, we test multiple clinically relevant and phylogenetically distinct Escherichia coli strains carrying extended-spectrum beta-lactamase (ESBL) or carbapenemase plasmids. While antibiotics influence the growth of incoming resistant strains, some are successful even without antibiotics. Growth outcomes depend on a combination of intrinsic growth capacities in relevant abiotic conditions, competition with resident E. coli, and strain-specific shifts in resident community composition. We also detect horizontal transfer of resistance plasmids in some conditions, but transconjugants remain rare across treatments. Here, we show that the success of antibiotic-resistant bacteria depends on strain-specific ecological interactions, helping to explain the spread and persistence of resistance in human microbiomes.