E. Coli receptor may explain why people fall ill when stressed

March 13th, 2009 - 1:48 pm ICT by IANS  

Washington, March 13 (IANS) A receptor known as QseE that resides in a diarrhoea-causing strain of E. Coli helps the pathogen make the host ill when it senses stress in the latter, says a new study.
A receptor is a molecule on the surface of a cell that docks with other molecules, often signalling the cell to carry out a specific function.

Vanessa Sperandio, study co-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,” 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 signalling between host and bacteria going on, and we have very little information about which bacteria receptors recognise the host and vice versa,” Sperandio said. “We’re scratching at the tip of the iceberg in our knowledge of this.”

In 2006, Sperandio’s lab was the first to identify the receptor QseC sensor kinase, a molecule found in the membrane of a diarrhoea-causing strain of E. Coli known as enterohemorrhaegic Escherichia coli, or EHEC.

Prior research by Sperandio has found that when a person ingests EHEC - which is usually transmitted through contaminated food such as raw meat - it travels peacefully through the digestive tract until it reaches the intestine.

There, chemicals produced by the friendly gastrointestinal microbial flora and the human hormones epinephrine and norepinephrine alert the bacteria to its location, said an UT-S release.

Once QseC recognises the stress hormones, it initiates a cascade of genetic activations in which EHEC colonises the intestine and moves toxins into human cells, altering the make-up of the cells and robbing the body of nutrients.

“The bacteria get what they want - nourishment - and the person ends up getting diarrhoea,” Sperandio said.

Previous research by Sperandio found that phentolamine, an alpha blocker drug used to treat hypertension, and a new drug called LED209 prevent QseC from expressing its virulent genes in cells. The next step is to test whether phentolamine has the same effect on QseE.

The study is available online in the issue of Proceedings of the National Academy of Sciences.

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