New Drug Class Shows Promise Against Legionnaire’s Disease

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 bacteria 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 in Australia, and Dr. Thomas Naderer and Ph.D. student Ms Mary Spier from the Monash University Biomedicine Discovery Institute, also in Australia, showed for the first time that a protein called BCL-XL is an Achilles' heel of Legionella-infected cells. Turning off BCL-XL with BH3-mimetic drugs killed the infected cells, allowing the infection to be cleared from the body. The research was published in the March 2016 edition of Nature Microbiology. The article is titled “Eliminating Legionella by Inhibiting BCL-XL to Induce Macrophage Apoptosis.” 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 legionnaires' 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.
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