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

Understanding the spread of antibiotic-resistant bacteria in human-associated microbial communities, particularly in the gut microbiome, is critical for combating the global resistance crisis. However, the role of various ecological factors, such as intraspecies or interspecies interactions, in modulating this process is poorly understood. We hypothesized that different strains within the same species would exhibit distinct interactions with the resident microbiota, leading to variable invasion outcomes. To test this, we examined the population growth of multiple clinically relevant antibiotic-resistant E. coli strains carrying ESBL and carbapenemase resistance plasmids. We introduced these strains into human gut microbiome samples from healthy individuals, using replicated anaerobic microcosms treated or untreated with antibiotics. We found that while antibiotic exposure significantly influenced the growth of these incoming strains, some were successful even in the absence of antibiotics. The variation in ecological success across strain-microbiome sample combinations was positively associated with the intrinsic growth capacities of the strains in local abiotic conditions and their competitive interactions with resident E. coli. Furthermore, the incoming resistant strains had strain- specific effects on the taxonomic composition of the resident microbiota; different strains not only varied in their growth performance in human microbiomes, in some cases they pushed taxonomic composition of the resident community in different directions. In contrast with phenotypes measured in gut microcosms, metabolic profiles measured across various single-carbon-source environments were not reliable predictors of population growth in human microbiomes. Overall, this controlled design reveals the multi-layered ecological dynamics and strain-specific mechanisms that govern the spread of antibiotic-resistant bacteria in individual human-associated microbiomes.