Friday, September 30, 2016

Brain-eating amoebas hunt brain chemical before they kill you

Electron micrograph showing amoebas in orange
Small but insidious

London School of Hygiene & Tropical Medicine/Science Photo Library

By Jessica Hamzelou

All it takes is a splash. Brain-eating amoebas can enter an unwary swimmer’s brain via their nose, and once that happens, their chances of survival are slim. “They have these food cups on their surface, which are like giant suckers,” says Francine Cabral of Virginia Commonwealth University in Richmond. “They’ll just start eating the brain.”

Now, researchers have discovered why this deadly amoeba has such an affinity for the brain – a breakthrough that could lead to life-saving drug treatments.

The amoeba, Naegleria fowleri (shown in orange in the picture above), tends to lurk in fresh water, although infections can also result from swimming in hot springs or improperly chlorinated pools. Of the 35 reported cases in the US between 2005 and 2014, there were only two survivors. Last month, a 19-year-old woman died after being infected in Maryland.

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After the amoeba enters the body, it bypasses the nose and related tissues and heads straight to the brain, where the first areas it destroys are the olfactory regions we use to smell, and parts of the frontal lobe, which are crucial for cognition and controlling our behaviour.

Chemical attractor

Why they specifically target the brain is a mystery. Abdul Mannan Baig at the Aga Khan University in Karachi, Pakistan, suspected the amoeba might be attracted to a chemical called acetylcholine or ACh, which is released in large amounts by cells at the front of the brain. This chemical is already known to act as a magnet for some immune cells and growing neurons.

To test this theory, Mannan looked for receptors on the amoeba that might attach to ACh. He and his colleagues started with Acanthamoeba – a similar genus that tends to infect people through skin wounds. The team isolated 126 proteins from the amoeba and ran them through a database to find other proteins with similar components or structures. One of these had a structure similar to the human receptor for Ach. The team have since repeated their search in Naegleria and found the same result.

This suggests that the amoebas have their own, ancient receptor for ACh, says Mannan. It is this attraction that probably causes the amoeba to bypass nasal tissues and head straight for the brain.

Cabral, who was not involved in the research, agrees that ACh could be the culprit, although she would like to see more evidence to support the theory. In her own work, she has seen how the amoebas race toward brain cells in a lab dish. “It could be ACh,” she says.

Mannan hopes that drugs that block the receptor could offer a new form of treatment for brain-eating amoeba infections. Such drugs already exist, and are used for treating irritable bowel syndrome or regulating heart rate, for example. Mannan is now testing them in mice infected with the amoeba.

But there’s one final hurdle. If these drugs can stop the amoeba from getting into the brain, they will have to be administered as soon as a person is infected, when the infection is all but impossible to diagnose. “Severe headache is usually the first sign, but by that point the amoeba is already in the brain,” says Cabral. “We need an early diagnostic test.”

This could become a more urgent problem in the coming years – infections are predicted to rise as the climate warms.

Journal reference: Journal of Receptors and Signal Transduction, DOI: 10.1080/10799893.2016.1217884

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