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Locusts engineered as biorobotic sensing machines

Sensors placed on the insect monitor neural activity while they are freely moving, decoding the odorants present in their environment. (credit: Baranidharan Raman)

Washington University in St. Louis engineers have developed an innovatiave “bio-hybrid nose” that could be used in homeland security applications, such as detecting explosives, replacing state-of-the-art miniaturized chemical sensing devices limited to a handful of sensors.

Compare that to the locust antenna (where their chemical sensors are located): “it has several hundreds of thousands of sensors and of a variety of types,” says Baranidharan Raman, associate professor of biomedical engineering, who has received a three-year, $750,000 grant from the Office of Naval Research (ONR).

The team previously found that locusts can correctly identify a particular odor, even with other odors present — and even in complex situations, such as overlapping with other scents or in different background conditions.

Replacing canines

In previous research, the opening of the locust maxillary palps to the trained odorant was used as an indicator of acquired memory. The palps were painted with non-odorous organic-chemical green paint to facilitate tracking. (credit: Debajit Saha et al./Nature Communications)

The ingenious idea in the new study by the Raman Lab is to remotely monitor neural activity from the insect brain while they are freely moving, exploring, and decoding the odorants present in their environment, which will require innovative low-power electronic components to collect, log, and transmit data.

The locusts could also collect samples using remote control. To do that, the engineers are developing a plasmonic “tattoo” made of a biocompatible silk to apply to the locusts’ wings. It will generate mild heat to help steer locusts to move toward particular locations by remote control. The tattoos, studded with plasmonic nanostructures, also can collect samples of volatile organic compounds in their proximity, which would allow the researchers to conduct secondary analysis of the chemical makeup of the compounds using more conventional methods.

“The canine olfactory system still remains the state-of-the-art sensing system for many engineering applications, including homeland security and medical diagnosis,” Raman said. “However, the difficulty and the time necessary to train and condition these animals, combined with lack of robust decoding procedures to extract the relevant chemical sending information from the biological systems, pose a significant challenge for wider application.

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This deadly soil bug can reach your brain in a day, end up in spinal cord

B. pseudomallei soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in Thailand and northern Australia (credit: Wikipedia CC)

Imagine a  deadly bacteria that can be picked up by a simple sniff and can travel to your brain and spinal cord in just 24 hours. Or one that could just be quietly sitting there, waiting for an opportune moment. Or maybe just doing small incremental damage ever day over a lifetime … as you lose the function in your brain incrementally.

That’s the grisly finding (in mice), published in Immunity and Infection this week, of a new study by Australian Griffith University and Bond University scientists.

The pathogenic bacteria Burkholderia pseudomallei, which causes the potentially fatal disease melioidosis, kills 89,000 people around the world each year and is prevalent in northern Australia, where a person with melioidosis has a 20–50 per cent chance of dying once it infects the brain. The bacterium is found in the northern parts of the Northern Territory, including Darwin.

In Southeast Asia 50 per cent of the population may be positive for melioidosis, and in places like Cambodia the mortality rate is as high as 50 per cent.

But for the rest of us, the findings could also lead to discoveries of how the common staphylococcus and acne bacterium also end up in the spinal cord, as well as how chlamydia travels to the brain in Alzheimer’s patients. Or even explain common back problems, which could be where bacteria have infected your bone, causing pain that could be simply treated with antibiotics, according to the researchers.

Tracing the bacteria in mice brains and spinal cords

(Top) A schematic drawing of a mouse brain showing the location of various images. (Bottom) D: A B. pseudomallei rod (arrow) present in trigeminal nerve near the connection between the trigeminal nerve in the brain and the brainstem. (E) B. pseudomallei rod (arrow) with a fluorescent particle (arrow with tail) after the merge between the trigeminal nerve and brainstem. Scale bars in μm. (credit: James A. St John et al./Infection and Immunity)

The olfactory mucosa, located in the nose, is very close to the brain and it has long been known that viruses could reach the brain from the olfactory mucosa. But researchers have not understand exactly how the bacteria traveled to the brain and spinal cord, or just how quickly.

To find out, James St. John, PhD., Head of Griffith’s Clem Jones Centre for Neurobiology and Stem Cell Research, and associates infected mice with B. pseudomallei. They were able to trace the bacteria travels from the nerves in the nasal cavity before moving to the brain stem and then into the spinal cord. (He noted that this could also be a pathway for many other common bacteria.)

“Our latest results represent the first direct demonstration of transit of a bacterium from the olfactory mucosa to the central nervous system (CNS) via the trigeminal nerve; bacteria were found a considerable distance from the olfactory mucosa, in the brain stem, and even more remarkably in the spinal cord,” said professor Ifor Beacham from the Griffith Institute for Glycomics.

Researchers will now work on ways to stimulate supporting cells that could remove the bacteria. St. John said the work was important because the bacteria had the potential to be used as a bioweapon and knowing how to combat it was extremely important.

“Bacteria have been implicated as a major causative agent of some types of back pain. We now need to work out whether the bacteria that cause back pain also can enter the brainstem and spinal cord via the trigeminal nerve,” he added.

Abstract of Burkholderia pseudomallei rapidly infects the brainstem and spinal cord via the trigeminal nerve after intranasal inoculation

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in south-east Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brainstem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brainstem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localised infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brainstem within 24 hours and then rapidly progressed over 2000 μm into the spinal cord. To rule out that the bacteria used a haematogenous route, we used a capsule-deficient mutant of B. pseudomallei, which does not survive in the blood, and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity.