Time to put TB on a diet

Tuberculosis is a highly contagious disease that spreads through the air via droplets of saliva. Although treatments exist for tuberculosis, new antibiotic-resistant strains are preventing TB from being eradicated. The goal is to find new ways to tackle the disease, which requires a thorough understanding of how the bacterium, known as Mycobacterium tuberculosis, behaves once it takes hold of the macrophages in our lungs. The team headed by Thierry Soldati, Professor at the Biochemistry department in UNIGE's Science faculty, has been working on a model system that acts like the macrophages in our immune system: the social amoeba Dictyostelium, a unicellular microorganism.

"We infected the amoebae with the Mycobacterium marinum bacterium, which induces tuberculosis in fish," explains Caroline Barisch, a researcher at UNIGE and the study's first author. "The pathogen behaves in the same manner as the TB bacillus, which means that we were able to use our simple and ethically responsible system to undertake experiments that could not be carried out directly on humans." Scientists had previously recognised that for the bacterium to survive, replicate and spread, it needed to consume the lipids that exist in the form of droplets in macrophages. Without this source of food, the bacillus cannot survive latently and wait for a weakness in the immune system in order to develop. It is well worth remembering that 30% of the world's population is infected by a dormant form of the TB bacillus.

The UNIGE biochemists observed the infection in vitro, analysing each stage of the process whereby the bacterium feeds on the lipids of its host. As Thierry Soldati explains: "We subsequently discovered that the mycobacterium can "reprogramm" the infected cell so that it diverts and attracts all the amoeba's fat reserves -- not just the lipid droplets but also the membranes -- so that it can feed on them." The researchers suppressed the lipid droplets of the host cells, the bacterium's preferred food source, and found that the bacterium has a back-up plan that allows it to compensate for this shortage by drawing on the lipids within the host's membranes. This shows that this lipid diet is most likely crucial for the survival of the bacterium.

"We now know that the bacillus is extremely 'addicted' to this high-fat food," continues Caroline Barisch. "Our current aim is to find a way to starve the bacillus by depriving it of access to the fat stores in our macrophages. The goal will be to target the enzymes of the bacillus and render them incapable of absorbing lipids." It is a discovery that opens the door to the prospect of new forms of treatment for neutralising the strains that are resistant to antibiotics.