Bioengineers aim to harness bacterial motion

By Kimberly Patch, Technology Research News

What bacteria do all day is sense chemicals. To survive they depend on hardwired chemical sensors, or chemoreceptors, that cause them to swim toward substances they need, and away from substances they don't like.

Researchers from Texas A&M University and the University of California at Los Angeles have modified the chemoreceptors of an E. coli bacterium to make it swim away from a substance it usually seeks out. At the same time, the researchers have worked out a way to change the bacteria's reaction to a given chemical, so that instead of controlling the direction the bacteria swims, a given chemical could turn on a gene that, for example, causes the bacteria to glow.

Being able to control both what a bacterium reacts to and its reaction will allow the tiny creature to eventually serve as an environmental sensor, said Manson. "You could use it to detect environmental toxins, pesticides, herbicides, heavy metals -- all kinds of stuff," he said.

For instance, "you can imagine scattering bacteria over a field which has been seeded with land mines, but nobody knows exactly where they are," said Manson. "Land mines leak TNT. So you would have spots of glowing bacteria where the TNT was leaking and therefore be able to identify where the land mine is."

The researchers have proved experimentally that they can modify bacteria chemoreceptors. There's still a lot of work to be done in order to produce bacteria that can sniff out TNT, however. The researchers are working to develop binding proteins for the chemoreceptors that will enable them to react to chemicals they don't normally recognize. They also have to demonstrate the rewiring changes that will turn on a gene once a bacterium's altered chemoreceptors sense a substance.

"We have to find out what genes we want to hook up to these promoters in order to give us signals that we can monitor. Once we've done that we [can] start engineering the binding sites," he said.

Changing the bacteria's reaction to a chemoreceptor hit will make it easier to see that the bacteria have sensed a substance, said Manson. "[It] will give you something you can measure -- either light production, antibiotic resistance or making an enzyme that will turn a chromogenic substrate blue or yellow," Manson said.

Eventually, different types of bacteria could be used to sense a series of substances and give a variety of responses, he said.

The ability to control bacteria's swimming motions is also potentially useful, said Manson. Since bacteria can be coaxed to move toward a certain chemical, they could eventually be used as tiny pack horses in nanofabrication or drug delivery applications, he said. "I can imagine medical uses where the cargo could be things that contain antibiotics or hormones or [chemicals] that would kill tumor cells," he said. The tiny delivery vehicles would move toward their targets by sensing a chemical at that location, which could be, for instance, a substance manufactured by tumor cells, he said.

The researchers are working toward this possibility with a project that will attach florescent beads two tenths of a micron in diameter to the bacteria, Manson said. A micron is one thousandth of a millimeter.

Although the group is working with E. coli bacteria, the work can eventually be transferred to other strains of bacteria that are not harmful to humans, Manson added.

The work is both novel and potentially useful, said Donna Marykwas, an assistant professor biological sciences at California State University at Long Beach. "E. coli has many different sensor kinase proteins that each detect different chemical and/or physical signals in the environment, and E. coli is just one bacterial species. Other bacteria have sensor kinases too, and so does the baker's/brewer's yeast S. cerevisiae. Therefore, many novel cell-based sensors can likely be made using this approach, and the sensitivity of these sensors is probably much greater than non-cell-based sensors engineered by man," she said

The technology could eventually be used to detect toxins in the environment, or in an engineered bacterium that could sense and swim towards a noxious chemical compound that it could metabolize into a less noxious substance, said Marykwas.

The researchers are also considering how to control bacteria's swimming motions to control fluid flow in tiny devices, Manson said.

"The way bacteria swim is by having helical spiral flagella which turn at their bases," he said. "If you grab hold of that helical flagellum and don't let it turn, then the cell body turns. So we can tie these guys down by their flagella to a surface and they spin. We have mutants that only spin one-way."

The trouble with fluid flow in tiny spaces is that as the diameter of a tube gets smaller, more pressure is needed to drive liquid through it. It takes less pressure to suck up liquid through a wide straw than a very narrow one, for instance, and the problems get much worse at the microscopic level. A group of spinning bacteria, however, could get things moving through a tube as small as a capillary, according to Manson. "If the bacteria are all turning in one direction they act like little turbines... and they'll cause flow," he said.

The physics works out well in computer simulations and the researchers are planning to make real world measurements with collaborators from the University of Arkansas this summer, Manson said. The ultimate goal of this line of research is to construct flagella-like motors by coaxing proteins to self-assemble into the proper shapes. "We're still trying to define how many proteins are needed to make the minimal motor, what kinds of solid supports we can use to adhere to the... motor and what additional factors... will be needed to get the motor proteins properly inserted, folded and assemble into a membrane," said Manson.

Bacteria could be used as bio detectors and to transport tiny materials in four or five years, said Manson. The flow generation work is likely to take longer, however "five years minimum, maybe close to... 10, maybe never if we are unlucky," he said.

Manson's research colleagues were Scott M. Ward of Texas A&M University and Asuncion Delgado and Robert P. Gunsalus of the University of California at Los Angeles. The research was funded by the The National Institutes Of Health (NIH) and the Army Research Office.

Timeline:   4-5 years, 5-10 years
Funding:   Government
TRN Categories:  Microfluidics and BioMEMS; Nanotechnology
Story Type:   News
Related Elements:  Technical paper, "Negative Chemotaxis to Nitrate/Nitrate Mediated by a NarX-Tar Chimera: Evidence for the Same Mechanism of Transmembrane Signaling by Bacterial Sensor Kinases and Chemoreceptors."


July 18, 2001

Page One

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Cartoons loosen up computer interfaces

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Bioengineers aim to harness bacterial motion

Lasers spin electrons into motion


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