The advance could lead to new treatment strategies for these infections, which can be fatal in people with compromised immune systems, researchers said. The study was conducted by scientists in the lab of Michael Manson, professor of molecular biosciences in the College of Natural Sciences.
The study results were published in the scientific journal Nature Microbiology.
The researchers were studying the evolution of bacteria when they began to examine an algal ancestor of Legionella and Coxiella. They realized that this ancient organism still exists within certain species of amoeba, which allowed them to look closely at how it interacts with its host.
"This discovery allowed us to see the mechanism of pathogenesis in real time, with atomic-level detail," said Manson.
Coauthor Amy Edwards, assistant professor of molecular biosciences, said the research could have profound implications for the field of microbiology and for the design of drugs used to target these infections.
"It changes the way we look at these organisms," Edwards said. "It highlights fundamental biology that underlies the survival of important human pathogens."
Legionella and Coxiella are the most common causes of waterborne bacterial pneumonia in the United States, causing life-threatening infections that require antibiotic therapy. Legionella is also the most common cause of hospital-acquired bacterial pneumonia.
To cause disease, Legionella and Coxiella must enter human cells and replicate within those cells. They do this using a specialized "type IV secretion system," a molecular machine that allows them to inject proteins into their host cells. This system is also used by other pathogens, including Chlamydia and pathogenic E. coli.
Using X-ray crystallography and electron microscopy, the researchers determined the precise molecular structure of the secretion system from the algal ancestor, enabling them to pinpoint its molecular target.
The results point to a possible therapeutic strategy for treating infections caused by Legionella and Coxiella: the development of drugs that inhibit the secretion system and prevent the bacteria from entering human cells.
"Small molecule inhibitors that target this secretion system could provide new therapies to treat or prevent devastating bacterial infections," Manson said.
The researchers are currently exploring potential drug candidates and hope to bring new treatment strategies into the clinic in the future.
