Legionella Pneumophila - Obtention of Nutrients

Obtention of Nutrients

Once inside the host-cell, Legionella needs nutrients to grow and reproduce. Inside the vacuole, nutrient availability is low, the high demand of amino acids by not covered by the transport of free amino acids found in the host cytoplasm. In order to improve the availability of amino acids, the parasite promotes the host mechanisms of proteasomal degradation. This generates an excess of free amino acids in the cytoplasm of L. pneumophila-infected cells that can be used for intra-vacuolar proliferation of the parasite.

To obtain amino acids, Legionella pneumophila uses the AnkB bona fide F-Box effector, which is farnesylated by the activity of three host enzymes localized in the membrane of the LCV ( Legionella containing vacuole): farnesyltransferase (FTase), Ras-converting enzyme-1 protease (RCE1), and isoprenyl cysteine carboxyl methyl transferase (IcmT). Farnesylation allows AnkB to get anchored into the cytoplasmic side of the vacuole.

Once AnkB is anchored into the LCV membrane, it interacts with the SCF1 ubiquitin ligase complex and functions as a platform for the docking of K48-linked polyubiquitinated proteins to the LCV. The K48-linked polyubiquitination is a marker for proteasomal degradation that releases 2 to 24 amino acid-long peptides, which are quickly degraded to amino acids by various oligopeptidases and aminopeptidases present in the cytoplasm. Amino acids are imported into the LCV through various amino acid transporters such as the SLC1A5 (Neutral amino acid transporter). The amino acids are the primary carbon and energy source of L. Pneumophila, that have almost 12 classes of ABC transporters, amino acid permeases, and many proteases, to exploit it. The imported amino acids are utilized by L. pneumophila to generate energy through the TCA cycle (Krebs cycle) and as sources of carbon and nitrogen.

However, promotion of proteasomal degradation for the obtention of amino acids may not be the only virulence strategy to obtain carbon and energy sources from the host. Type II–secreted degradative enzymes may provide an additional strategy to generate carbon and energy sources.