Virginia technical researchers have learned how bacteria can manipulate molecules to infect host organisms.
Daniel Capellot and his research team have discovered a mechanism by which the bacterial pathogen Shigella Flexneri, the causative agent of dysentery, manipulates molecular activity to ensure survival against the host’s natural defenses. Their findings were recently published in Structure, a Cell Press Journal that supports Open Access.
“This infection strategy could be adopted by other bacteria, and this study is a potential foundation for understanding the molecular mechanisms underlying various bacterial infections,” says Capelto, an associate professor of biological sciences.
Understanding the specific ways in which a typical bacteria progresses can help researchers more accurately target precautions that interrupt the process.
To survive, bacteria infect the host by replicating themselves, infecting cells, and escaping those infected cells. A typical example of this process is seen in Shigella Flexneri, a bacteria that is transmitted via contaminated water or food, and is targeted to the intestinal layer.
According to Capelto, dysentery is common in low- and middle-income countries, especially among children under the age of five, and is responsible for 160,000 deaths worldwide each year.
“Pathogens such as bacteria infect cells, which change the metabolism they are infected or the behavior of the cells they are infected in order to prepare them for their invasion,” said Capelto, an affiliate of the Flarin Life Sciences Institute. “Bacteria release a variety of protein bundles, and those proteins begin to ruin the host, allowing the bacteria to survive under hostile circumstances.”
Bacterial proteins disrupt host metabolism homeostasis or balance, causing an acidic environment, and produce large amounts of lipids that are usually present in the traces of host cells.
In healthy organisms, specific proteins, Tom1 and Tollip, serve the ability to deliver membrane proteins that are not needed for degradation. However, when disrupted under bacterial infections and acidic conditions, Tom1 and possibly Tollip are sequestered within cells by binding to bacterial-producing lipids, promoting the survival of infected cells, allowing the bacteria to progress the infection cycle.
“We used high-resolution biochemical and biophysical tools to identify lipid binding sites in Tom1, providing evidence that this mechanism prevents Tom1 from functioning properly,” Capelluto said.
Finding the sites where important binding occurs is fundamental to understanding this bacterial infection route and may provide insights to unravel other bacterial infection routes.
In the future, Capelt aims to continue this research at a different level.
“It’s nice to do some kind of research on a cellular level, and that’s what we’re going to do next,” Capelto said.
Capelluto’s Virginia Technology Research Team included the following members:
