In this article tells us about a newly discovered receptor in a strain of Escherichia coli. This new receptor can be blocked to avert infection, according to the research study. It is believed that a finding like this might aid in developing better therapies, specifically those to treat bacterial infections resulting in common diseases like food poisoning, diarrhea or plague.
According to the article, it is the researchers at the UT Southwestern Medical Center who are the first to identify the receptor. This receptor is known as QseC. According to the researchers of such E. coli receptor, it is found to be 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 and in the issue of the Proceedings of the National Academy of Sciences, the researchers described just how they used phentolamine to intervene with the signaling to the receptor. This phentolamine is actually an alpha-blocker drug that is being used to treat hypertension. In this study, phentolamine is utilized to successfully impede signaling to the receptor. Without such signals to the receptors of E. coli, it is found that the bacteria then pass blindly through the digestive tract without infecting the microscopic cells.
According to Dr. Vanessa Sperandio who is the senior author of the study and assistant professor of microbiology at UT Southwestern, this receptor is commonly found in many pathogens. He further advices that we can use this knowledge to design specific antagonists to block many types of bacterial infections.
In the article, it further explains that prior research done by Dr. Sperandio found that when a person ingests the more virulent enterohemorrhagic E coli, also known aso EHEC, it travels peacefully through the digestive tract until reaching the intestine. EHEC is usually transmitted through contaminated food such as raw meat according to the researchers of the study. However, there are chemicals produced by the gastrointestinal microbial flora and the human hormones called the epinephrine and the norepinephrine are responsible for alerting the bacteria to its location.
According to the researchers, this cellular cross talk is responsible for triggering a cascade of genetic activations prompting EHEC to colonize and translocate toxins into cells. This in turn results in the alteration of the makeup of the microscopic cells and robbing the body of nutrients. As explained in the article too, an infected person may develop bloody diarrhea or even hemolytic uremic syndrome. These symptoms are known to be capable of causing death especially in cases of people with weak immune systems, the elderly and young children.
This new study identifies QseC as the specific receptor by which EHEC senses the signals. AS explained in the article, when the receptor binds to signaling molecules, the bacterium can infect the microscopic cells in the body.
Researchers of this study tested the capacity of adrenergic antagonists. Adrenergic antagonists include drugs such as alpha and beta-blockers. According to the article, the capacity of such drugs to disrupt the receptors sensing ability was tested. The researchers of the study found that phentolamine binds to the QseC receptor. They further have found that it occupies the pocket that the receptor would use to recognize the host epinephrine and norepinephrine signal, thus in turn resulting to the blocking of the QseC receptor from sensing the signals and preventing it from being able to express its virulence genes in cells.
According to Dr. Sparandio, it is believed that this knowledge opens the door to further understanding of the signaling processes between microbes and humans. It further gives way to the development of novel treatments of bacterial infections with antagonists to these signals.
According to the article, new therapies are important because treating some bacterial infections with conventional antibiotics can actually cause the release of more toxins and may even result to the worsening of the disease outcome.
That importance is magnified because of the QseC receptors 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 diseases mentioned are all emerging infectious diseases. These are the types of diseases that afflict thousands of people each year in the whole world according to the Centers for Disease Control and Prevention.
Dr. Sperandio further explains in the article that the overuse of antibiotics has led bacteria to develop resistance to antibiotics. He adds that as a result of such condition, a novel type of therapy is needed.
Other UT Southwestern researchers who were also involved in the study were first author Dr. Marcie B. Clarke. Dr Clarke is a graduate of the molecular microbiology program who now works in a Boston patent law firm. David T. Hughes is also a researcher in the study. He is a molecular microbiology graduate student. Researchers from the University of Maryland School of Medicine also were involved in this said study pioneered by Dr. Sperandio.
Original Text:
http://www.utsouthwestern.edu/utsw/cda/dept37389/files/300707.html
