Unveiling the role of Ecological Interactions in Antibiotic Resistance Evolution via Horizontal Gene Transfer

forthcoming

Horizontal Gene Transfer (HGT) stands among the most common mechanisms for the emergence and persistence of Antibiotic Resistance (AR) in microbial communities, a major challenge in medicine and agriculture. While molecular mechanisms driving HGT are typically studied through in vitro co-cultures of two species, a donor and an acceptor species, HGT occurs in nature within microbial communities (such as the human gut microbiome) in which such two species interact with many others. Metagenomics has identified these ecological interactions as potential catalysts for HGT, yet direct experimental evidence remains lacking. This project aims to elucidate how ecological interactions drive HGT of AR genes in diverse bacterial communities by combining experiments and theoretical models. Recent experimental advances have enabled the ecological interrogation of highly diverse communities in vitro, while theoretical models, inspired by statistical physics, can disentangle the dominant ecological interactions and predict the community dynamics. I will use high-throughput, in vitro techniques to assemble hundreds of different synthetic communities in which we will measure the rates of HGT of AR genes, both in the presence and absence of antibiotic exposure. I will develop a novel theoretical model that incorporates species interactions, environmental context and HGT. Utilizing statistical physics tools, I will generate testable predictions capable of interpreting the experimental outcomes. The project aims to generate a novel, quantitative understanding of how ecology modulates the HGT of AR genes, bridging the gap between molecular mechanisms previously described in pairwise co-cultures and ecological trends inferred from metagenomics. This knowledge will not only lead to the development of a theoretical framework integrating community ecology and HGT but also has the potential to indicate new strategies for addressing the global antibiotic resistance crisis.