Why are people sick when stressed?

A newly discovered receptor in Escherichia coli may help explain why people are often weaker when they are stressed.

Researchers at UT Southwestern Medical Center are the first to identify the receptor, called QseE, in the flow of E. coli causing diarrhea. This receptor recognizes the stressful signal from a host of bacteria and helps the pathogen to grow that the host is ill. The receptor is a molecule on the cell's surface that lies with other molecules, often signaling the cell to perform a certain function.

The study is published online in the journal Proceedings of the National Academy of Sciences. Dr. Vanessa Sperandio, professor of microbiology at UT Southwestern and principal author of the study, said QseE is an important factor in the development of the disease because the signals it recognizes from the host, primarily is epinefrin and phosphate, often accompanied by blood poisoning or infection.

Dr. Sperandio said: 'Patients with high intestinal phosphate levels are more likely to get infections due to infection of intestinal bacteria. If we can understand how bacteria recognize these signs, we can find ways to intervene in that process and prevent infection '.

Millions of harmful bacteria exist in the human body, waiting for a signal from the host to release their toxins. Without these signals, the bacteria will pass through the digestive tract without infecting cells. The problem is that we have yet to find a way to prevent the release of bacterial toxins.

Dr. Sperandio explains: 'Of course there are many chemical signals between hosts and bacteria, and we have very little information about which microbial receptors identify the host and vice versa. Our knowledge of this issue is very limited. '

In 2006, Dr. Sperandio's laboratory first recognized the QseC receptor, a molecule found in the E Coli membrane that causes diarrhea called enterohemorrhagic Escherichia colim or EHEC. Earlier research by Dr. Sperandio found that consuming EHEC - usually through contaminated food such as fresh meat - it moved normally through the gastrointestinal tract to the intestine. There, chemicals are produced by the stomach bacteria and hormones epinefrin and norepinefrin in humans signal bacteria.

Dr. Vanessa Sperandio. (Photo: UT Southwestern Medical Center)

When QseC recognizes stress hormones, it starts activating a series of genes, whereby EHEC will "settle" in the intestine and introduce toxins into human cells, altering the genetic structure and nutritional properties of body '

Dr. Sperandio said: 'Bacteria have what they want - nutrition - and we have diarrhea'.

The new study identified QseE, a receptor only found in intestinal bacteria. This receptor ends the activation created by QseC. It also regulates time for bacterial activity, including controlling the genes needed for EHEC to cause diarrhea.

Dr. Sperandio said: 'EHEC needs both agencies to feel right to become really toxic. When people are stressed, they often excrete epinefrin and norepinefrin. Both hormones activate the receptor QseC and QseE. Therefore, when you are stressed, you activate the bacterial infection '.

Dr. Sperandio said the findings also show that there is much to learn about the genetic level of stress-induced diseases.

She added: 'The problem may not only be a stress signal that weakens your immune system, but you are also nurturing some pathogens. This is a double-edged sword. You have a weakened immune system and pathogens that exploit that weakness. '

Previous studies by Dr. Sperandio found phentolamine, a drug used to treat hypertension, and a new drug called LED209 that prevents QseC from expressing its viral genes in cells.

The next step is to check whether phentolamine is effective for QseE.

Nicola Reading, a former graduate student at UT Southwesterm, is the lead author of the study. Dr. David Rasko, former professor of microbiology at UT Southewestern, currently at the University of Maryland, and Dr. Alfredo Torres from UT Branch in Galveston also contributed to the study.

The research was funded by the National Institutes of Health, Ellison Medical Foundation and the Burroughs Foundation.