Researchers at UT Southwestern Medical Center identified a receptor, known as QseE, which resides in a diarrhea-causing strain of E coli. The receptor senses stress cues from the bacterium’s host and helps the pathogen make the host ill. A receptor is a molecule on the surface of a cell that docks with other molecules, often signaling the cell to carry out a specific function.
Dr. Vanessa Sperandio, associate professor of microbiology at UT Southwestern and the study’’ senior author, said QseE is an important player in disease development because the stress cues it senses from a host, chiefly epinephrine and phosphate, are generally associated with blood poisoning, or sepsis.
“Patients with high levels of phosphate in the intestine have a much higher probability of developing sepsis due to systemic infection by intestinal bacteria,” Dr. Sperandio said. “If we can find out how bacteria sense these cues, then we can try to interfere in the process and prevent infection.”
Millions of potentially harmful bacteria exist in the human body, awaiting a signal from their host that it’s time to release their toxins. Without those signals, the bacteria pass through the digestive tract without infecting cells. What hasn’t been identified is how to prevent the release of those toxins.
“There’s obviously a lot of chemical signaling between host and bacteria going on, and we have very little information about which bacteria receptors recognize the host and vice versa,” Dr. Sperandio said. “We’re scratching at the tip of the iceberg on our knowledge of this.”
“When people are stressed they have more epinephrine and norepinephrine being released. Both of these human hormones activate the receptors QseC and QseE, which in turn trigger virulence. Hence, if you are stressed, you activate bacterial virulence.” Dr. Sperandio said the findings also suggest that there may be more going on at the genetic level in stress-induced illness than previously thought.
“The problem may not only be that the stress signals are weakening your immune system, but that you’re also priming some pathogens at the same time,” she said. “Then it’s a double-edged sword. You have a weakened immune system and pathogens exploiting it.”
Previous research by Dr. Sperandio found that phentolamine, an alpha blocker drug used to treat hypertension, and a new drug called LED209 prevent QseC from expressing its virulence genes in cells. Next she will test whether phentolamine has the same effect on QseE.
Full press release: Researchers probe mechanisms of infection