People become infected with Legionella bacteria by inhaling contaminated water droplets. The bacteria hide within human cells called macrophages, escaping the body’s own immune defenses and being shielded from many types of antibiotics.
Inside the macrophage, the bacteria change the compostion of proteins within their host cell. Intriguingly, they drain their host of a protein MCL-1 that helps body cells to stay alive. Another such protein is BCL-XL, which is still present in infected macrophages.
Researchers including from the Walter and Eliza Hall Institute and Monash University discovered this to be a potential Achilles' heel of the bacteria.
In a paper published in Nature Microbiology, the researchers show that they could completely obliterate Legionella-infected cells by treating them with 'BH3-mimetic drugs that switch off BCL-XL.
BH3-mimetics drugs were initially developed to treat cancer, by targeting ‘survival’ proteins such as BCL-XL and MCL-1 that make cancer cells immortal.
Importantly, while infected macrophages were killed, the BH3-agents used left uninfected macrophages untouched.
The researchers believe that BH3-mimetics could become a valuable new line of treatment for Legionella and potentially other bacteria that hide out within cells. This could also help address an emerging problem of bacteria becoming increasingly resistant to available antibiotics.
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