The gene variants that lead to Gaucher disease helps immune cells kill tuberculosis bacteria, at least in zebrafish
, can survive inside lysosomes, allowing the infection to spread within macrophages in the lungs.
There are several hundred mutations that cause Gaucher disease, but they all result in a kind of fat building up within lysosomes. at the University of Cambridge and her colleagues investigated the effect of these mutations in zebrafish, which are sometimes used to study TB, as they develop a similar illness when infected withThe team gave the fish the commonest mutations that cause Gaucher disease in Ashkenazi Jews. As expected, fat built up within the lysosomes of their macrophages.
By two measures, the fish were less susceptible to infection. For instance, in a test that involved injecting them with one bacterium, 42 per cent of the mutated animals stayed uninfected compared with 13 per cent of fish without the mutations. “The host has a higher chance of killing the bacteria,” says Ramakrishnan.
Further experiments showed that the type of fat that builds up inside lysosomes is toxic to both human TB bacteria and the fish equivalent, when grown in a dish. “The accumulation of this fat has a detergent activity. It [disrupts] the membranes of the TB bacteria,” says Ramakrishnan.
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