Researchers at UT Southwestern Medical Center are the first to identify the receptor, known as QseC, used by a diarrhea-causing strain of E coli to receive signals from human flora and hormones in the intestine and express virulence genes to initiate infection.
In a study made available online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences, researchers describe how they used phentolamine, an alpha blocker drug used to treat hypertension, to successfully impede signaling to the receptor. Without such signals, bacteria then pass blindly through the digestive tract without infecting cells.
"This receptor is found in many pathogens, so we can use this knowledge to design specific antagonists to block bacterial infections," said Dr. Vanessa Sperandio, senior author of the study and assistant professor of microbiology at UT Southwestern.
Prior research by Dr. Sperandio found that when a person ingests the more virulent enterohemorrhagic E coli, or EHEC – which is usually transmitted through contaminated food such as raw meat – it travels peacefully through the digestive tract until reaching the intestine. There, however, chemicals produced by the friendly gastrointestinal microbial flora and the human hormones epinephrine and norepinephrine alert the bacteria to its location.
This cellular cross talk triggers a cascade of genetic activations prompting EHEC to colonize and translocate toxins into cells, altering the makeup of the cells and robbing the body of nutrients. An infected person may develop bloody diarrhea or even hemolytic uremic syndrome, which can cause death in immune-weakened people, the elderly and young children.
The new study identifies QseC as the specific receptor by which EHEC senses the signals. When the receptor binds to signaling molecules, the bacterium can infect cells.
Researchers tested the capacity of adrenergic antagonists, drugs such as alpha and beta blockers, to disrupt the receptor's sensing ability. They found that phentolamine binds to the QseC receptor and occupies the pocket that the receptor would use to recognize the host epinephrine and norepinephrine signals – thus blocking the QseC receptor from sensing the signals and preventing it from being able to express its virulence genes in cells.
This knowledge opens the door to further understanding of the signaling processes between microbes and humans and to the development of novel treatments of bacterial infections with antagonists to these signals, Dr. Sperandio said.
New therapies are important because treating some bacterial infections with conventional antibiotics can cause the release of more toxins and may worsen disease outcome.
That importance is magnified because of the QseC receptor's existence in other types of bacteria, including, Shigella, which causes dysentery; Salmonella, which causes food poisoning and gastroenteritis; and Yersinia, which causes bubonic plague. Those are all emerging infectious diseases that afflict thousands of people each year in the United States and worldwide, according to the Centers for Disease Control and Prevention.
"Overuse of antibiotics has led bacteria to develop resistance to antibiotics, so a novel type of therapy is needed," Dr. Sperandio said.
Cliff Despres | EurekAlert!
Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Physics and Astronomy
20.11.2018 | Medical Engineering
20.11.2018 | Physics and Astronomy