Metabolic Remodeling of Microbes By Obligate Intracellular Parasites Alters Species Ratios in Microbial Communities

Bacteria carry a diversity of extrachromosomal genetic elements, including plasmids and some types of bacteriophage (viruses that infect bacteria). Because these genetic elements are obligate intracellular parasites, often dependent on host metabolic processes for replication and proliferation, infection by both plasmids and phage can change host metabolism, driving infected cells into physiological states distinct from uninfected cells. Yet little is known about how infection by these intracellular parasites impacts microbial community composition and function through changes to cellular metabolism. Here we integrate a genome-scale metabolic modeling approach with an in vitro system to investigate the consequences of two intracellular parasites of Escherichia coli - the plasmid F’ and the filamentous phage M13 - on interactions between bacteria in a multispecies community composed of cross-feeding strains of E. coli, Salmonella enterica, and Methylorubrum extorquens. In silico experiments suggest that intracellular parasites drive changes in growth rate and cellular excretion that alter community composition in a predictable way across a range of microbial interaction types. In vitro, we find that, when bacterial species are engaged in obligate mutualism, infection by either the F’ plasmid or by both parasites increases species evenness, as predicted by our models. Our work therefore provides a foundation for predicting and managing microbial community composition and function for both biomedical and bioengineering applications.