How tuberculosis bacteria manage to survive inside body’s macrophage cells

The bacterium Mycobacterium tuberculosis is a successful organism that lives in an estimated one third of the world's population. But only about five percent of those infected develop the disease.

"We also know that many people do not become infected despite exposure to the infection. This is a question we are looking for an answer to," says Amanda Welin, who is now presenting her doctoral dissertation in medical microbiology.

The research group has studied phenomena in both the bacterium and the macrophage, whose task is to knock out infectious substances that get into the body.

One weapon is enzymes, which make the ingested bacteria feel sickly. Enzymes work best in acidic environments, with a pH level under 6. For their part, the bacteria can strike back by releasing substances that prevent the pH level from going down. Amanda Welin has shown that this warfare is directly reflected in the growth or reduction of bacteria.

These bacteria also have a capacity to kill macrophages and spread to new cells. Welin shows that this is done by having a tiny protein cause cell death, necrosis, which in turn leads to inflammation of the tissue.

To carry out these studies, Amanda Welin and her colleagues developed a new method for determining the number of bacteria inside a cell. They use a gene from sea-fire organisms, which cause strange lights in seawater at night. When this gene is added to the genes of the bacterium, the bacterium begins to produce the same luminescent substance, luciferase, as the sea-fire organism does. Thanks to this, it's possible to monitor developments inside the macrophage -- the intensity of the light radiating outward corresponds to the number of bacteria inside. If their number grows, this indicates that they have begun to multiply inside the human cell.

The method can be used to search for plausible drug candidates. In that field, the Linköping scientists are collaborating with a group of colleagues in Sudan, who are testing, among other things, various medicinal plants with substances that could possibly be used as active ingredients to combat tuberculosis.