Metabolic remodeling of microorganisms by mobile genetic elements alters mutualistic community composition

Mobile genetic elements (MGEs) are ubiquitous in prokaryotes and exert significant influence on microbial communities, in part through their effects on host metabolism. While some MGEs directly alter host metabolism by introducing novel enzymes, all MGEs can indirectly change bacterial metabolism by redirecting intracellular host resources away from native bacterial processes toward MGE production. As a result, even when MGEs do not provide new metabolic functions, their carriage can influence host traits such as growth rate, nutrient uptake, and waste excretion, with consequences for how bacteria contribute to community and ecosystem functions. However, there are few empirical tests of how the indirect metabolic consequences of MGE carriage shape interactions between host and non-host bacterial species. We integrated genome-scale metabolic modeling with an <i>in vitro</i> obligate cross-feeding system to investigate the metabolic consequences of two MGEs in <i>Escherichia coli</i>: the conjugative plasmid F128 and the filamentous phage M13. We examined the impact of these MGEs on interactions between bacteria in a multispecies cross-feeding community composed of <i>E. coli</i>, <i>Salmonella enterica,</i> and <i>Methylobacterium extorquens</i>. Both modeling and <i>in vitro</i> experiments suggested that MGE carriage can change the growth rate and excretion profile of <i>E. coli</i>. We also found that indirect changes to host metabolism induced by our MGEs increased the density of cross-feeding species. Our work emphasizes that microbes carrying MGEs can have different metabolisms than MGE-free cells, even when MGEs do not encode metabolic enzymes, and demonstrates that these metabolic shifts can have significant consequences for microbial community structure and function.IMPORTANCEMobile genetic elements (MGEs) often shape the structure and function of microbial communities by influencing the metabolism of bacterial cells. Though some MGEs change metabolism directly by transferring genetic material that provides access to novel niche space, all MGEs should alter host metabolism indirectly to some degree by shifting intracellular metabolic processes toward MGE replication. This study uses a combination of flux balance analysis and an <i>in vitro</i> system consisting of <i>Escherichia coli</i>, <i>Salmonella enterica</i>, <i>Methylobacterium extorquens</i>, and two MGEs in <i>E. coli</i> to investigate how MGEs change the community contributions of their hosts via metabolic conflict alone. Flux balance analysis suggests that MGEs can change intracellular demand for different metabolic processes, leading to shifts in the identities and concentrations of compounds that hosts externalize into the environment. This finding is supported by experimental results and extends our understanding of how MGEs shape the structure and function of microbial communities.