Metabolic remodeling of microorganisms by obligate intracellular parasites alters mutualistic community composition

Abstract

Bacteria carry many types of obligate intracellular parasites, including plasmids and bacteriophage. During infection, these parasites redirect intracellular resources away from bacterial processes toward parasite production. Because parasite-induced metabolic changes influence host traits such as growth rate, nutrient uptake, and waste excretion, parasitic infection should alter how microbes contribute to important community and ecosystem functions. Yet there are few empirical tests of how infection shapes metabolically-mediated interactions between host and non-host species. Here, we integrated a genome-scale metabolic modeling approach with an in vitro obligate cross-feeding system to investigate the metabolic consequences of two intracellular parasites of Escherichia coli: the conjugative plasmid F128 and the filamentous phage M13. We examined the impact of these parasites on interactions between bacteria in a multispecies community composed of E. coli, Salmonella enterica, and Methylobacterium extorquens. Modeling predicted that parasitic infection of E. coli should have consequences for host growth rate and the secretion and reuptake of carbon byproducts. These theoretical results aligned broadly with in vitro experiments, where we found that parasitic infection changed the excretion profile of E. coli, inducing the net externalization of lactate. We also found that parasite-driven changes to metabolism increased the density of cross-feeding species and changes to community composition were generalizable across community interactions and some host and parasite genotypes. Our work emphasizes that microbes infected by obligate intracellular parasites have different metabolisms than uninfected cells and demonstrates that these metabolic shifts can have significant consequences for microbial community structure and function. IMPORTANCEThe intracellular parasites of bacteria shape the structure and function of microbial communities in a variety of ways, including by killing their hosts or transferring genetic material. This study uses a combination of flux balance analysis and an in vitro system consisting of Escherichia coli, Salmonella enterica, Methylobacterium extorquens, and two intracellular parasites of E. coli, the F128 plasmid and the filamentous phage M13, to investigate how parasites change the community contributions of their hosts via metabolic remodeling. Flux balance analysis suggests that parasites change intracellular demand for different metabolic processes, leading to shifts in the identities and concentrations of compounds that infected hosts externalize into the environment. This finding is supported by experimental results, which additionally show that infection can induce the production of lactate. These findings extend our understanding of how bacteriophage and plasmids shape the structure and function of microbial communities.