New drug class offers potential new treatment for lethal bacteria

March 7, 2016, Walter and Eliza Hall Institute
New drug class offers potential new treatment for lethal bacteria
Dr James Vince and colleagues have revealed a potential new treatment for certain bacterial infections.

A new class of drugs has shown promise for treating the bacteria that cause legionnaires' disease, a potentially fatal lung infection.

The discovery that 'BH3-mimetic' drugs obliterate cells infected with Legionella could lead to new treatments for a variety of bacterial infections, even those that are resistant to antibiotics.

A research team including Dr James Vince of the Walter and Eliza Hall Institute, and Dr Thomas Naderer and PhD student Ms Mary Spier from the Monash University Biomedicine Discovery Institute, showed for the first time that a protein called BCL-XL is an Achilles' heel of Legionella-. Turning off BCL-XL with BH3-mimetic drugs killed the infected cells, allowing the infection to be cleared from the body. The research is published in the March edition of Nature Microbiology.

People become infected with Legionella bacteria by inhaling contaminated water droplets, often from cooling towers or spas, or contaminated soil such as potting mix. The bacteria hide within human cells called macrophages, escaping the body's own immune defenses and being shielded from many types of antibiotics. People with a weakened immune system, including the elderly, are at particular risk of the serious lung Legionella infection called legionairres' disease.

Dr Vince said that soon after infecting a macrophage, Legionella bacteria alter the composition of proteins within their host cell to prevent the host from detecting the infection. "We were particularly interested that this drained the macrophage of a protein called MCL-1, that helps to keep cells alive," he said. "The 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," Dr Vince said.

BH3-mimetics drugs were initially developed to treat cancer, by switching off 'survival' proteins such as BCL-XL and MCL-1 that make cancer cells immortal.

"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," Dr Vince said. "Walter and Eliza Hall Institute scientists have spent three decades deciphering how 'survival proteins' including BCL-XL keep cells alive, and how this can be exploited to treat cancer. This is the first time BH3-mimetics have been used to successfully treat bacterial infections."

With the emergence of antibiotic-resistant strains of bacteria now posing a serious global health risk, new treatments for bacterial infections are urgently needed.

"In the future we are hopeful that BH3-mimetics may be a valuable new line of treatment for Legionella and other bacteria that similarly hide out within ," Dr Vince said.

Explore further: Researchers discover new way to screen for cancer-killing drugs

More information: Mary Speir et al. Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis, Nature Microbiology (2016). DOI: 10.1038/nmicrobiol.2015.34

Related Stories

Researchers discover new way to screen for cancer-killing drugs

February 3, 2016
A technique called "mito-priming" is the latest method to be developed by researchers in the fight against cancer.

Researchers study how cancer cells respond to Mcl-1-inhibitory BH3-mimetics

October 2, 2014
The European pharmaceutical company Servier has established a collaborative partnership with the Walter and Eliza Hall Institute to facilitate the development of new agents that could be effective in treating several types ...

New agents show promise for treating aggressive breast cancers

July 18, 2011
Some of the most aggressive forms of breast cancer are more vulnerable to chemotherapy when it is combined with a new class of anti-cancer agent, researchers from the Walter and Eliza Hall Institute have shown.

Detailed studies reveal how key cancer-fighting protein is held in check

May 15, 2014
St. Jude Children's Research Hospital scientists have mapped the structural details of how p53 attaches to its regulatory protein, called BCL-xL, in the cell. The protein p53 is a key activator of the cell's protective machinery ...

Recommended for you

Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs

June 14, 2018
Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June ...

3-D imaging and computer modeling capture breast duct development

June 14, 2018
Working with hundreds of time-lapse videos of mouse tissue, a team of biologists joined up with civil engineers to create what is believed to be the first 3-D computer model to show precisely how the tiny tubes that funnel ...

Beating cancer at its own game with a Trojan horse telomerase

June 13, 2018
Telomerase is a reverse transcriptase that uses an RNA template to synthesize telomeres. These repeat sequences bind special proteins that fold the ends of chromosomes back onto themselves to create a stable cap. When this ...

Turning the tables on the cholera pathogen

June 13, 2018
Recent cholera outbreaks in regions that are ravaged by war, struck by natural disasters, or simply lack basic sanitation, such as Yemen or Haiti, are making the development of new and more effective interventions a near-term ...

Troves from a search for new biomarkers: blood-borne RNA

June 12, 2018
It's the critical first step in treating everything from strokes to cancer: a timely and accurate diagnosis. Today, doctors often rely on biomarkers, such as cardiac troponin, the protein that appears in the blood after a ...

High-tech treatment of open leg wounds no better than using regular dressings: study

June 12, 2018
A new study of open leg fractures suggests there is no difference to patient recovery whether high-tech negative pressure wound therapy devices are used, compared to standard dressings.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.