Anti-cancer drugs eliminate Legionnaires' disease

Cancer drugs have shown potential after being repurposed to fight the bacteria responsible for Legionnaires’ disease. 

The disease is a form of bacterial pneumonia with the Gram-negative bacteria infecting the person’s macrophages and lung epithelial cells. Using BH3-mimetic drugs, researchers were able to destroy cells that had been infected with the Legionella bacteria, through targeting a protein called BCL-XL.

Dr James Vince, from the Walter and Eliza Hall Institute in Australia, said: “The [Legionella] bacteria inadvertently leave BCL-XL as the only survival protein keeping the cell alive - a single point of failure at the molecular level.

“We exploited this vulnerability by treating Legionella-infected cells with BH3-mimetic drugs that switch off BCL-XL. These agents could specifically kill the infected macrophages, leaving uninfected macrophages untouched — exactly what you would want to happen if you were treating an infected person,” he added.

BH3-mimetics were originally created to fight cancer as they target proteins such as BCL-XL and MCL-1 that enable cancer cells to survive apoptosis – programmed cell death.

Legionnaires’ disease is contracted by inhalation of water contaminated with the Legionella bacteria with more than 90% of cases caused by Legionella pneumophila. The disease is more commonly contracted by those aged over 50 or those suffering from chronic respiratory or renal illnesses.

Dr Vince continued, “We were really excited to discover that BH3-mimetics can be used to treat serious Legionella lung infections, killing the infected cells and allowing the bacteria to be cleared from the body. This is the first time BH3-mimetics have been used to successfully treat bacterial infections.”

It is hoped that NH3-mimetics may be a line of treatment for Legionella and other bacteria that hide within cells, such as Chlamydia and mycobacterium tuberculosis.

The research can be found in Nature Microbiology.