November 23, 2011 | 2
Bacteria have adapted to live in many niches; from the environmental bacteria that live in the soil and the seas, to the highly specialised intracellular bacteria that rely exclusively on their surrounding host for nutrients. While all bacteria face challenges in adapting their environment to suit them, intracellular bacteria face a particularly interesting challenge, as they must adapt to the conditions inside a living creature without killing their host.
All living organisms require a source of carbon, nitrogen and oxgyen in order to survive. Most organisms, particular the multicellular ones, prefer to use glucose or glycogen as a source of carbon, but some bacteria have found alternative ways of surviving. The bacteria Legionella pneumophila, which can live inside human or amoeba cells and is the cause of Legionnaires disease, gets its energy sources from the amino acids that make up proteins. Essentially, it lives on the Atkins diet, consuming high levels of protein and much lower levels of carbs.
There are amino-acids floating around inside eukaryote host cells, but they tend to be at low concentrations. In order to get more of the amino-acids it requires the Legionella actively encourages the eukaryotic host cell to start breaking down its own proteins. The breakdown of proteins is a normal process that happens within your cells everyday as the making and breaking of proteins is vital for producing chemical signals and modifying metabolic pathways. The bacteria latch onto this system and start running it for their own ends.
To break down proteins a human (or amoeba) cell sticks a little label onto them, a small chemical molecule called ubiquitin (which I will just notate as U for now). A protein that needs to be removed will be marked with these little U tags, which are a signal for other controlling proteins to manhandle the doomed molecule over a big molecule called the proteosome, which breaks it down.
The legionella gets into the cell wrapped in a little protective coat of outer cell membrane. Once inside this vacuole, it starts making itself at home, secreting around 300 proteins into its surrounding host in order to make itself a proper niche to live in. Included amongst these proteins is one called AnkB, which anchors itself into the vacuole membrane, facing out into the host cell. The AnkB itself doesn’t appear to add U-tags to the proteins, but it seems to strongly encourage the existing host tagging machinery to go overboard with the U-tags.
These tagged proteins are then degraded by the host-cell machinery providing the perfect environment for the Legionella to live in. If the gene for AnkB is knocked out, the bacteria suffers severe growth defects, which can be partially recovered by carefully feeding the bacteria with a mixture of amino-acids allowing it to grow again. In mice models, bacteria with the AnkB gene knocked out were incapable of causing the bacterial pulmonary disease altogether.
Furthermore, this is not a species specific response either. Using the host-degradation machinery to provide the bacterial Atkins diet is common in infected organisms from humans and mice right down to amoeba. Finding a single gene of such importance may prove a major help for vaccine and drug development in the future.
University of Louisville Press Release.
Price CT, Al-Quadan T, Santic M, Rosenshine I, & Abu Kwaik Y (2011). Host Proteasomal Degradation Generates Amino Acids Essential for Intracellular Bacterial Growth. Science (New York, N.Y.) PMID: 22096100