How Tuberculosis and Leprosy Invade Cells

Picture: Mycobacterium tuberculosis

Mycobacterium tuberculosis
bursts forth and multiplies quickly

The tuberculosis (TB) bacterium Mycobacterium tuberculosis follows a different path in the host cell than its weaker younger brother Mycobacterium bovis (BCG), used as TB vaccine.

The absorption of bacteria into cells is also known as fagocytose and is the process whereby the membrane of a cell envelopes the bacterium thus forming a pustule (fagosome) within the cell in which the enveloped bacterium can be securely stored.

Once inside the body BCG is stored in the fagosome but within two days the contagious TB bacterium bursts through the membrane wall of the fagosome. The bacterium falls freely into a cell landing in a food-rich environment where it rapidly multiplies. The researchers at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital demonstrated how the leprosy bacterium burst forth in a similar way. Mycobacterium leprae is a sister of the TB bacterium.

Till now scientists thought that the fagosome acted as a reservoir whence not only the BCG vaccine but also the contagious bacterium slowly multiplied. Now, however, not only does it appear that the bacterium follows an entirely different path but also multiplies quicker when lying free inside the cell.

The researchers discovered that when bursting out the TB bacterium that causes illness and the leprosy bacterium are able to cut the membrane wall of the fagosome. Whilst carrying out a double blind test they were able to establish that the RD1 area was involved in the process. This is where the bacterium genes lie that can cut through the membrane wall. Whilst mutating in the RD1 area the bacterium remained imprisoned in the fagosome but when the mutation was artificially repaired the bacteria were once again able to break loose.

This discovery has consequences when developing new medicines. The current BCG vaccine provides little protection because it provokes a weak immunological reaction. In contrast the TB bacterium provokes a strong immunological reaction through its alternative path.; Source: Netherlands Cancer Institute