Feast or famine: the host-pathogen battle over amino acids

Abstract

Intracellular bacterial pathogens often rely on their hosts for essential nutrients. Host cells, in turn, attempt to limit nutrient availability, using starvation as a mechanism of innate immunity. Here we discuss both host mechanisms of amino acid starvation and the diverse adaptations of pathogens to their nutrient-deprived environments. These processes provide both key insights into immune subversion and new targets for drug development.

Fig. 1.

Three bacterial strategies for evading amino acid starvation. Chlamydia trachomatis responds to amino acid starvation by differentiating to aberrant reticulate bodies, viable but metabolically inactive forms that can differentiate back to active forms when amino acid become available again. While Mycobacterium tuberculosis faces amino acid starvation during infection, its constitutive expression of amino acid synthesis makes it generally resistant to host-driven starvation. Legionella pneumophila exploits host proteins to override starvation and deliver free amino acids into its intracellular niche. AnkB, a secreted virulence factor, drives the polyubiquitination of LCV membrane proteins. The host proteasome is then recruited to proteolyze ubiquinated targets, producing free amino acids that are transported into the LCV by the upregulated host transporter, SLC1A5.