Pathogen Effects on Energy Metabolism in Host Cells

Pathogens reprogram host cell metabolism toward different metabolic pathways depending on the pathogen and host cell type. In addition, metabolic fuel is a prerequisite for the proliferating immune cells and their functional responses. Several bacteria also actively respond to the nutrient status of host cells by transforming to diverse types of altered metabolic forms such as dormant or persistent forms. These various metabolic states of bacteria contribute to antibiotic resistance and chronic infections, which are important clinical problems. The molecular pathways behind the essential metabolic changes in most pathogens and their host cells can be attributed to genetic modifications. However, in case of the obligate intracellular bacteria such as the Chlamydia spp., where genetic modification is limited, alternative techniques have to be used to characterize host and pathogen metabolic interaction. Two-photon fluorescence lifetime imaging microscopy (FLIM) of the metabolic coenzymes, NAD(P)H, allows for independent characterization of Chlamydia and host cell metabolic changes in living cells. The metabolic changes of Chlamydia during the developmental cycle can be monitored in real time by quantifying the fluorescence lifetime of protein-bound NAD(P)H and its relative amount in ratio to free NAD(P)H. Importantly, the technique provides a power tool for visualizing persistent infections in living cells and compartmentalized characterization of the metabolic changes in the host cell (e.g., cytosol, mitochondria, and nucleus).