LSU Vet Med faculty receive NIH R21 award to study Rickettsia bacteria

Investigating how Rickettsia bacteria manipulate cell stress responses to cause disease

Co-principal investigators in the LSU Vet Med Department of Pathobiological Sciences Juan Martinez, Ph.D., and Basel Abuaita, Ph.D., have received an R21 award from the National Institutes of Health. This research examines how disease-causing Rickettsia bacteria exploit a cell's natural stress-response machinery to survive and multiply, with the goal of identifying new targets for future treatments.

Rickettsia are bacteria that can only survive and reproduce inside living cells. Some species, including those that cause Rocky Mountain spotted fever and other spotted fever illnesses are transmitted by ticks in many regions of the United States and can make people seriously sick.

Once these bacteria enter the body after a tick bite, they invade cells and take over some of the cell's normal functions to help themselves survive and multiply. Researchers have discovered that Rickettsia bacteria appear to exploit a natural cellular process called the endoplasmic reticulum (ER) stress response. This system normally helps cells cope when proteins are not being folded or processed correctly.

The study focuses on a key protein called IRE1α, which acts like a cellular alarm system during stress. Early evidence suggests that Rickettsia species that cause disease in mammals activate this pathway and use it to create a more favorable environment for their growth. When researchers blocked IRE1α with drugs in laboratory experiments, the bacteria were much less able to reproduce inside both immune cells and blood vessel cells.

Despite these findings, scientists still do not fully understand how Rickettsia manipulate these stress-response pathways or how important they are in causing disease.

This project will investigate two main questions:

• How do ER stress pathways, especially those controlled by IRE1α, help Rickettsia grow inside infected cells?
• How does altering these stress responses affect the bacteria's ability to survive, spread, and cause disease in animals?

The researchers hope that understanding how Rickettsia hijack the cell's stress-response system could reveal new ways to prevent or treat infections caused by these bacteria.