Metabolic crosstalk between host and pathogen: sensing, adapting and competing

Key Points During an infection the metabolic networks of the host and the bacterial pathogen become interlinked. These interactions between the host and pathogen metabolism influence both bacterial virulence and host responses, which determine the outcome of infection. Bacterial pathogens use metabolic cues provided by the host microenvironment to evaluate their location and alter their gene expression and metabolic networks. These cues can be induced directly by the invading pathogen or are provided by environment-specific metabolites. The host immune response detects metabolites produced by invading pathogens and expresses effector mechanisms that poison bacteria-specific metabolic pathways. Recently defined 'virulence genes' of pathogens include modified or expanded metabolic networks that evade immune mechanisms. Bacterial pathogens and mammalian cells use similar metabolic pathways that share intermediates. The overlap between these networks is a potential source of competition between the host and pathogen during infection. Amino acids, such as tryptophan, asparagine and arginine, are particularly important nutrients that are central to the host–pathogen interaction. Host metabolic diseases, such as diabetes mellitus, increase the risk of bacterial infections, and the interlinked metabolism between the host and pathogen may act as a target for therapeutic intervention. Therefore, modulating host metabolic pathways is a promising approach to treat infections. The metabolism of pathogens and hosts are intertwined — they compete for resources, sense metabolites produced by each other and target metabolic processes to mediate virulence and immunity. In this Review, Olive and Sassetti discuss the emerging roles of metabolism in host–pathogen interactions. Our understanding of bacterial pathogenesis is dominated by the cell biology of the host–pathogen interaction. However, the majority of metabolites that are used in prokaryotic and eukaryotic physiology and signalling are chemically similar or identical. Therefore, the metabolic crosstalk between pathogens and host cells may be as important as the interactions between bacterial effector proteins and their host targets. In this Review we focus on host–pathogen interactions at the metabolic level: chemical signalling events that enable pathogens to sense anatomical location and the local physiology of the host; microbial metabolic pathways that are dedicated to circumvent host immune mechanisms; and a few