This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: When it comes to invading healthy cells, Legionella bacteria rely on blending in rather than breaking in. New research from Van Andel Institute scientists demonstrates how a protein produced by Legionella mimics the behavior of the host cell's own proteins.
This mechanism allows the protein, RomA, to change how the host's genes are regulated and create conditions that help the bacteria survive and multiply. But there is a limit to RomA's effectiveness. Although the protein can read and respond to the host's existing epigenetic landscape, those same signals constrain what RomA can and cannot do.
The result is a biological trade-off: By taking its cues from the host cell, Legionella can exploit its epigenetic machinery but also becomes subject to the host's rules. "What makes these findings so exciting is that they reveal a two-way conversation between host and pathogen that we didn't fully appreciate before," said Evan Worden, an assistant professor in VAI's Department of Structural Biology and corresponding author of the study. "We knew bacteria like Legionella can manipulate host cells' physiology, but we didn't know that cells' existing epigenetic landscape puts guardrails around what the pathogen can do.
Understanding this nuanced interaction gives us a better picture of how these infections work and offers new avenues for developing improved therapies." Legionella is best known for its role in Legionnaires' disease, a severe type of pneumonia caused by inhaling water droplets containing the bacteria. Once in the lungs, Legionella burrows into immune cells called macrophages, turning them into refuges that help the bacteria survive and multiply. The bacteria's ability to live inside host cells makes Legionella and other intracellular pathogens difficult to treat.
The study, published in the Proceedings of the National Academy of Sciences, provides the first evidence that bacterial effector proteins like RomA can be influenced by the host's existing epigenetic landscape. Epigenetics controls which genes are "on" or "off" without altering the underlying DNA sequence. To do this, epigenetics relies on chemical tags to govern how DNA is packaged and accessed.
What makes RomA's behavior particularly striking, Worden said, is that bacteria and human cells organize and regulate their DNA in fundamentally different ways. Human DNA is precisely packaged within a cell's nucleus, where it wraps around spool-like histone proteins to form a structure called chromatin. Bacteria lack a nucleus and a chromatin-based organizational system.
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