Feeding Uninvited Guests: mTOR and AMPK Set the Table for Intracellular Pathogens

Most pathogenesis studies focus on pathogen virulence attributes that mediate host colonization, toxicity, or immune evasion. Some studies focus on how pathogens employ active mechanisms to acquire essential nutrients such as iron and vitamins from the host by producing siderophores or avidins. In order to prevent pathogen nutrient acquisition, host cells employ a process called nutritional immunity to sequester these nutrients, particularly iron, from invading pathogens [1]. However, relatively little attention has been paid to understanding the mechanisms by which pathogens parasitize energy and catabolic substrates from the host even though several host and pathogen metabolic genes, including those in central carbon metabolism, are regularly identified as required for growth in the host [2,3]. This issue is particularly important for intracellular pathogens that must compete with the host cell for energy and nutrient sources. How and where do intracellular pathogens obtain sufficient amounts of energy and nutrients to support their replication? Pathogens may either parasitize existing energy stores or manipulate the host cell to create usable energy and anabolic precursor metabolites. Several recent studies have identified the host AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) kinases as two important regulators of cellular metabolism whose activities are often altered during infection. However, the AMPK/mTOR pathway also regulates autophagy, which can destroy cytosolic pathogens. While the evasion of autophagy by pathogens is well appreciated, recent work suggests that both the AMPK/mTOR pathway and autophagy itself can provide intracellular metabolites that support intracellular pathogen replication.