Host Delivery of Favorite Meals for Intracellular Pathogens

Pathogens grow and cause disease by exploiting the host as a rich and diverse source of food. However, it is not always an easy task to tap these food resources since the host innate immune response restricts pathogen access to crucial nutrients (“nutritional immunity”) [1]. Pathogens have acquired various mechanisms to evade host nutritional innate immunity and to trigger the host to generate additional preferable sources of carbon, nitrogen, and energy. Pathogens utilize various nutrients at vastly different rates. Some nutrients such as metal ions, cofactors, and monomeric components of proteins, lipids, and carbohydrates are directly incorporated into biomass. In addition, pathogens need to degrade substantial amounts of nutrients to small excreted waste products in order to obtain the energy they require for assembling biomass components and maintaining homeostasis (such as counteracting dissipation of membrane gradients). Uptake and metabolism of such energy sources is generally much faster compared to nutrients that are directly incorporated into new biomass. While extracellular pathogens can often exploit rich energy sources delivered to them by the host circulation, intracellular bacterial pathogens depend on their surrounding host cells for supply of energy sources at sufficiently high rates. This extensive metabolic interplay between host cells and the pathogens that they nurture is likely full of fascinating, rich biology. However, these major fluxes remain poorly characterized since common methods to study pathogen metabolism such as tracking incorporation of isotope-labelled carbon/nitrogen into biomass are not informative on nutrients converted into excreted waste products. On the other hand, new approaches start to unravel how intracellular pathogens acquire energy sources at sufficiently high rates for growth and disease—in particular, intravacuolar pathogens that must import nutrients across the vacuolar membrane. This Pearl article will highlight acquisition of energy sources by intravacuolar pathogens and its role in disease. For other aspects of microbial nutrition in vivo and host mechanisms for nutrient restriction, the reader is referred to various recent reviews [2–5].