Could magnetic bacteria be the next generation of microbots?

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The cutting edge of robotics may not be a smarter Siri or a less-creepy humanoid Japanese robot. It might be a swarm of bacteria, compelled to do our bidding through a remotely controlled magnetic field.

Some of the biggest technological advances of the past two decades have involved scaling things down. The development and continual improvement of microprocessors has revolutionized home computing. And the emerging field of nanomedicine promises to transform biomedical science in many ways: from targeted drug delivery to tissue repair at the cellular level.

However, working at the microscale (thousandths of a millimeter) or nanoscale (millionths of a millimeter) poses major challenges. To create a circuit out of microscopic components, we need very small tools that can do the work for us. We need microscopic robots, or microbots.

Artist's depiction of a nanobot performing cell surgery. Credit:

Artist’s depiction of a nanobot performing cell surgery. Source: yalescientific.org 

But building useful microbots is no easy task. Power supply has always been one of the toughest challenges. Some bots contain a very lightweight battery. Others possess a coin cell that scavenges vibrational or light energy from its surroundings. Telling our microbots where to go is another hurdle. Microbots typically don’t work alone- we usually need a swarm of them to perform a task. And we’d like to be able to direct that swarm with the utmost precision.

Some scientists think the solution to our microbot woes can be found in nature. Bacteria are essentially organic “machines” that use light or chemical energy to move about and do work. They fit the size criteria, and they’re everywhere. Rather than re-invent the wheel, what if we could train bacteria to do work for us?

To answer this question, microroboticists are now looking to a group of bacteria that possesses an astounding property: magnetism.

So-called magnetotactic bacteria are promising because their motion can be guided by an externally applied magnetic field. Given the right magnetic field, we might be able to coordinate the motion of thousands to millions of magnetotactic bacteria at once.

Source: iGEM2009

Source: iGEM2009

Magnetotactic bacteria are a genetically diverse group of organisms thought to have evolved during the early Proterozoic, some 2.5 billion years ago, when rising atmospheric oxygen concentrations were reducing the amount of dissolved iron in Earth’s oceans. It’s believed this caused some bacteria to start stockpiling iron. Eventually, these iron stores were adapted to form magnetosomes, crystalline structures found in the cell membranes of modern magnetotactic bacteria.  Magnetosomes align in a chain, allowing the bacterium to orient itself like a compass needle to the local magnetic field.

The most obvious advantage to a magnetotactic microbot is that its motion can be guided by a user-generated magnetic field. But bacteria are also advantageous because they possess flagella. These rotating, tail-like structures act as a propeller, allowing bacteria to swim about quickly and change direction with ease. And the energy required to turn a flagellum is generated by the bacterium’s own metabolism. Power source, check. Motor, check.

Helicobacter pylori electron micrograph, showing multiple flagella on the cell surface Electron micrograph of H. pylori possessing multiple flagella (negative staining). Credit: Wikipedia

Helicobacter pylori electron micrograph, showing multiple flagella on the cell surface Electron micrograph of H. pylori possessing multiple flagella (negative staining). Credit: Wikipedia

So, what’s it going to take for magnetotactic bacteria to become our microbots of choice? One challenge scientists are now focusing on is 3-D aggregation. Using a single electromagnet, it’s simple business to line a bunch of magnetic bacteria up in a 2-D sheet. Forming a 3-D swarm is more challenging. But if doable, 3-D configurations would have major advantages. A 3-D swarm would be much easier to guide through the intricacies of the human vascular system. It would also be able to build 3-D objects more efficiently.

In a paper recently published in the Journal of International Robotics Research, scientists used Magnetococcus marinus, a spherical, magnetotactic bacterium possessing 2 bundles of flagellar “propellors”, to explore the possibility of creating 3-D bacterial clusters with magnets.

Using remotely powered pairs of electromagnetic coils, the researchers applied three different time-varying magnetic field sequences to a liquid culture of M. marinus. They were able to generate both 2-D and 3-D bacterial configurations. Then they managed to steer these swarms through a complex network of glass tubes intended to mimic capillaries.

These basic steps are laying the foundation of being able to one-day guide armies of magnetotactic bacteria to carry out many tasks. In the future, swarms of magnetic “biobots” might be used for targeted cancer treatments, transporting microscale objects, assembling microcircuits, and even microscale magnetic resonance imaging.

ResearchBlogging.org

de Lanauze, D., Felfoul, O., Turcot, J., Mohammadi, M., & Martel, S. (2013). Three-dimensional remote aggregation and steering of magnetotactic bacteria microrobots for drug delivery applications The International Journal of Robotics Research, 33 (3), 359-374 DOI: 10.1177/0278364913500543

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From farm to table: insects as a conduit for antibiotic resistant bacteria

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The love affair between industrial agriculture and the antibiotic industry has come into an uncomfortable spotlight of late. In 2011, 7.7 million pounds of antibiotics were sold to treat sick people in the United States. This compares with a whopping 29.9 million pounds of antibiotics fed to cattle, pigs and poultry.1 Regular antibiotics doses keep perpetually overcrowded animals from falling ill and dying en masse, but antibiotics are also widely used to hasten growth, shortening an animal’s time to slaughter and increasing profit.

Concentrated animal feeding operations, or CAFOs, have come to dominate the meat industry over the past fifty years. Swine operations such as the one depicted here represent an enormous source of environmental pollution and are a breeding ground for antibiotic resistant bacteria. Credit: Wikimedia commons

Concentrated animal feeding operations, or CAFOs, have come to dominate the meat industry over the past fifty years. Swine operations such as the one depicted here represent an enormous source of environmental pollution and are a breeding ground for antibiotic resistant bacteria. Credit: Wikimedia commons

What’s the consequence of all this unfettered antibiotic use? Multi-drug resistant strains, or “superbugs” are on the rise. Our ability to keep pace with resistance by producing new antibiotics is diminishing. It’s even been suggested that we’re now entering a post-antibiotic era.

In 2010, representatives of the FDA, U.S. Department of Agriculture and Center for Disease Control and Prevention testified before Congress that a definitive link exists between the overuse of antibiotics in animal agriculture and antibiotic resistant diseases in humans.

Credit: pewhealth.org

Credit: pewhealth.org

But in spite of mounting evidence, the meat industry has largely succeeded in lobbying against any antibiotic restrictions. A major thrust of the industry’s argument is the lack of direct evidence linking antibiotic resistant bacteria bred on animal farms to human disease.

Now, proponents of antibiotic regulation may have some powerful new evidence to fuel their case. Microbial ecologist Ludek Zuerkand colleagues at Kansas State University are finding that insects- particularly houseflies and cockroaches- may represent the missing link between animal farms and human population centers.

Their review paper on insects and antibiotic resistance is currently in press in the journal Applied and Environmental Microbiology.

Zurek’s research team focuses on Enterococci, a group of bacteria responsible for illnesses ranging from urinary-tract infections to meningitis. Enterococci are also rather infamous for developing multi-drug antibiotic resistance. In one study, researchers measured the abundance of Enterococci in two swine production facilities in Kansas and North Carolina. The scientists examined houseflies, roaches and pig feces collected at both sites, finding Enterococci in 89% of all samples. Multi-drug resistant strains were found everywhere. Moreover, the drug-resistant strains found in flies and roaches were genetically identical to the strains found in swine feces, indicating insects acquired their pathogens from pigs.

In another study, the researchers screened houseflies collected from five fast food restaurants in a town in northeastern Kansas. Ninety seven percent of flies harbored Enterococci. The most abundant strain, Enterococcus faecalis, showed resistance to broad-spectrum antibiotics including tetracycline, erythromycin, ciprofloxacin and kanamycin. The scientists also identified transposons– snippets of DNA bacteria can swap during conjugation, their version of sex- that are associated with antibiotic resistant traits.

Ready-to-eat food from the same restaurants was also contaminated with antibiotic-resistant bacteria. Contamination was higher in summer than winter, corresponding with increased numbers of houseflies in restaurants.

From these investigations, the researchers concluded that “food served in restaurants is commonly contaminated with antibiotic-resistant Enterococci and that houseflies may play a role in this contamination.”

The common housefly may be more than just a nuisance: new research highlights this insect's important role in spreading antibiotic resistant bacteria.

The common housefly may be more than just a nuisance: new research highlights this insect’s important role in spreading antibiotic resistant bacteria. Credit: Wikimedia commons

Not wishing to lose points for a lack of thoroughness, the scientists decided to test directly whether insects from animal farms can contaminate food. In another study, they collected flies from a cattle feedlot and brought them back to the lab. Within thirty minutes, the flies deposited roughly 1,000 antibiotic-resistant Enterococci on a hapless beef patty. This experiment was carried out using as few as five flies.

Houseflies give bacteria more than just a free ride from farm to food. They may also serve as an incubator. Several studies have shown that pathogenic strains of E.coli proliferate in the gut of common houseflies and can be transferred during feeding.

Using a fluorescent protein to tag and track bacteria, Zurek’s research team found Enteroccoccus density peaks in the fly’s crop, or foregut, roughly 48 hours after ingestion. Significantly, houseflies regurgitate the contents of their crop while feeding. In doing so, they can disseminate bacteria into their food and water.  Zurek suggests houseflies serve as a “bioenhanced vector for bacteria” because of their dual role as incubator and locomotion.

The work of Zurek and his fellow scientists has profound public health implications.  Through many lines of evidence, this body of research demonstrates a direct link between the antibiotic resistant bacteria on factory farms and antibiotic resistant bacteria in our food.

Of course, none of this is terribly surprising, is it? We’ve known since biblical times that flies are harbingers of disease. Included in the ten Biblical Plagues in the Book of Exodus is the Plague of Flies, which “came [as a] grievous swarm of flies into the house of Pharaoh, and into his servants’ houses, and into all the land of Egypt: the land was corrupted by reason of the swarm of flies.”

 However, when it comes to an issue as personal (and political) as food, we sometimes tend to forget unpleasant truths. In his book in Eating Animals, an acclaimed work of investigative journalism on the modern meat industry, Jonathan Safran Foer writes, “Food choices are determined by many factors, but reason (even consciousness) is generally not high on the list.” As hard scientific evidence accumulates on the link between antibiotic resistance on animal farms and public health, one can only hope growing consumer consciousness will force the meat industry to take a hard look at its practices.

1. Pew Campaign on Human Health and Industrial Farming

ResearchBlogging.org

Zurek, L., & Ghosh, A. (2014). Insects Represent a Link between Food Animal Farms and the Urban Environment for Antibiotic Resistance Traits Applied and Environmental Microbiology, 80 (12), 3562-3567 DOI: 10.1128/AEM.00600-14

 

 

Geobacter, the microbe electric, uses biotic nanowires to breathe iron

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Geobacter metallireducens, an iron breathing bacteria

Geobacter metallireducens, an iron breathing bacteria

While it is hard for most of us to imagine life without oxygen, bacteria have been finding other ways to breathe for billions of years. A particularly successful group of anaerobic (non-oxygen breathing) bacteria is the Geobacter. From acid mine drainage sites to iron-rich rocks buried meters beneath the Earth and rusting ship wreckage on the ocean floor, Geobacter specialize in environments inhospitable for most life. How do they do so? For one, Geobacter don’t need oxygen. They can “breathe” using a number of other elements, including iron, sulfur and uranium. Recently, another startling feature of Geobacter was discovered that may shed light on their success as iron-breathers. They are electrically conductive.

Before we get to electrical conductivity, a bit of background on iron breathing, or “iron reducing”  in technical lingo. All life on earth requires energy. On a molecular level, all life acquires energy in much the same way: stripping electrons from one substance (usually, but not always, carbon) and transferring said electrons to another substance- an electron acceptor. Oxygen is the preferred electron acceptor among multicellular organisms because of its high electron affinity. This just means you get more “bang for your buck” using oxygen to strip electrons off your food than using, say, iron or sulfur. But oxygen is not found everywhere, and many microbes have become adapted to using other electron acceptors in lieu of oxygen. In theory, this makes sense. In practice, iron is a bit of a head-scratcher. In its oxidized (i.e., electron-depleted) form, iron is a heavy, insoluble metal that cannot easily cross cell membranes. For decades, scientists have assumed that iron-reducers like Geobacter have some adaptation that allows them to use iron outside of their cells for respiration.

Long appendates (pili) on Geobacter allow them to conduct electrons to heavy metals in their environment

Long appendates (pili) on Geobacter allow them to conduct electrons to heavy metals in their environment

This is where electricity comes in. Like many bacteria, Geobacter has long, filamentous appendages called pili extending from its body. Pili allow bacteria to sense their environment, similarly to whiskers or antennae. Sometimes, bacteria use pili to directly interact with their environment, releasing chemical compounds or exchanging genetic information with other bacteria. It turns out Geobacter’s pili are highly electrically conductive- as conductive as synthetic organic metals. This discovery has led scientists to hypothesize Geobacter’s pili serve as “electrical wires” that conduct electrons from inside the cell to iron in the environment.

Genetic studies have provided substantial evidence to support the “nanowire” hypothesis. The pilA gene encoding pili proteins is more highly expressed when Geobacter is grown with insoluble iron than soluble iron. That is, there is a direct relationship between pili production and the presence of iron that cannot cross cell membranes. To obtain direct evidence that pili are involved in iron respiration, scientists have created “knockout” strains of Geobacter that lack the pilA gene. Sure enough, pilA knockouts cannot respire insoluble iron, but they still grow using soluble iron that can diffuse across their cell membranes. Experimental evidence from culture studies also supports the link between electrical conductivity and pili. When grown in environments where electrical conductivity may provide an advantage, such as on graphite electrodes, Geobacter produce more pili.

A microbe with metallic conductivity is more than just a curious oddity of nature. Geobacter’s conductive pili raise exciting prospects for engineers in the emerging field of bioelectronics, who envision creating nano-powergrids out of “microbial wires”. Geobacter grown on electrodes may one day serve as a cheap energy source- if we can find a way to harness that energy.