A new class of drugs has shown promise for treating the bacteria that causes Legionnaires’ disease, which is a potentially fatal lung infection. The discovery that ‘BH3-mimetic’ drugs obliterate cells infected with Legionella bacteria may lead to new treatments for a variety of bacterial infections, including those resistant to antibiotics. According to a Science Daily news report, the research team showed for the first time that a protein called BCL-XL is an Achilles’ heel of Legionella-infected cells. The turning off of BCL-XL with BH3-mimetic drugs killed the infected cells, which allowed the infection to be cleared from the body.
People become infected with Legionella bacteria by inhaling contaminated water droplets or contaminated soil, and the bacteria hide within human cells called macrophages. James Vince, PhD, a member of the research team, explains that soon after infecting a macrophage, Legionella bacteria change the composition of proteins within their host cell to prevent the host from detecting the infection. Vince says, “We were particularly interested that this drained the macrophage of a protein called MCL-1, that helps to keep cells alive. The bacteria inadvertently leave BCL-XL as the only survival protein keeping the cell alive — a single point of failure at the molecular level.”
Vince adds that the researchers exploited this vulnerability by treating cells infected with Legionella 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,” states Vince. He says the research team was excited to discover that BH3-mimetics could be used to treat severe Legionella lung infections by killing the infected cells and allowing the bacteria to be cleared from the body.
“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,” Vince says. “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 cells.”
Photo Credit: Walter and Eliza Hall Institute, Australia
Source: Science Daily