The clustered sensors may work together in teams to amplify faint food "smells" into strong commands that make the germs swim toward dinner.

The study, published in today's issue of the journal Proceedings of the National Academy of Sciences, found possible solutions to two long-standing mysteries in a bacterial behavior called chemotaxis, which is the ability to sense changes in concentrations of food chemicals and then swim toward the food.

Scientists discovered in 1993 that chemical sensors known as receptors were clustered near the ends of Escherichia coli bacteria and not uniformly distributed on the bacterium's surface, as originally believed. It had been thought that uniformly distributed sensors would make bacteria more efficient at detecting food chemicals.

The chemical sensors on E. coli are incredibly sensitive. For example, a bacterial cell has roughly 1,000 receptors that can detect serine, an amino acid that serves as one of several food sources for bacteria. An E. coli bacterium can sense serine if just one of those 1,000 receptors comes in contact with serine, or detect the change if the number of sensors in contact with serine increases by one, say from 997 to 998.

The mystery is how the receptors amplify such a weak chemical signal into a much stronger signal that orders the bacterium's flagella -- six tail-like structures that act like propellers -- to rotate the proper way so the bacterium swims toward food.

In the new study, University of Utah biologists John S. Parkinson, Peter Ames and colleagues found that the two mysteries are logically related.

By creating mutant bacteria, they found evidence that the receptors are grouped into teams of three. Those teams, in turn, cluster together and act as a "league" of many teams, amplifying the incoming "smell" signal many times, thereby causing the cell's "propellers" to spin appropriately.

Parkinson, a professor of biology, said the findings are relevant not only for understanding how simple bacteria like E. coli move, but for shedding light on similar behaviors in more complicated cells. For example:

* White blood cells "fight infections by migrating to a wound or source of infection by sensing bacterial waste products or byproducts of inflammation," Parkinson said.

* Sea urchins and certain other sea creatures release sperm into seawater, and the sperm sense chemicals emitted by sea urchin eggs to find, swim toward and fertilize the eggs. There is some evidence, albeit controversial, that human sperm sense chemicals from human eggs to swim toward and fertilize the eggs.

"All living organisms are aware of their environment, and they respond to changes in their environment in adaptive ways -- they move, they grow, they eat, they develop, they sense environmental information to control their lives," Parkinson said. "For example, most organisms -- even bacteria -- can sense sound, light, pressure, gravity and chemicals."

He said biologists study E. coli because they represent "the simplest example of how cells detect and respond to their environment -- something that all living cells do. The more we understand about bacteria and how they detect and respond to their environment, the more we appreciate how sophisticated very 'simple' organisms can be. If we can't understand a bacterium, what hope is there to understand something much more complicated, like our own cells?"

E. coli have five different kinds of sensors or "chemoreceptors" they use to detect food. The food-sensing receptors extend from outside the bacterial cell to inside the cell. The outside portion detects food chemicals. The inside portion sends chemical signals via messenger proteins within the bacterial cell to E. coli's flagella -- the propellers.

When a bacterium's receptors sense increasing concentrations of food chemicals, the propellers rotate counterclockwise, which makes the bacterium continue on its course toward its dinner. If the concentration of food decreases, the propellers reverse, causing the cell to change direction until it again senses that it is swimming toward a food source.

The new study dealt with only two of the five kinds of chemical sensors on E. coli -- those that detect the amino acids serine and aspartate.

When a food chemical attaches or "binds" to a receptor, it only stays there for one-thousandth of a second. The mystery has been how such a brief, weak connection between a food chemical and perhaps one out of 1,000 sensors on the bacterium is amplified into a much stronger signal to control the bacterium's propellers and movements.

The study found evidence that a bacterium's sensors work together in teams of three, and that the clusters of sensors at the ends of a bacterium represent a "league" of receptor teams working together.

Ames, Parkinson and colleagues performed the study by creating mutant E. coli in which the receptors ranged from highly clustered to uniformly distributed. They found that mutant bacteria without clustered sensors could not swim toward serine, which suggested that clustering might enable the sensors to work together to send signals to the propellers.

The biologists measured the food-seeking ability of the bacteria by placing them on agar -- a nutrient-rich gelatin -- within flat petri dishes. The bacteria eat serine within the agar and begin to grow. When nearby serine food is all eaten, normal bacteria swim toward serine farther away, causing the round bacterial colony to expand across the plate.

The mutant bacteria, however, could not swim directly toward more food, so the mutant colonies remained small and dot-shaped. The mutant bacteria sort of "staggered around and didn't spread out much," Parkinson said.

The biologists also found that when they mutated the bacteria's serine sensors, the bacteria also could not swim toward aspartate, even though the aspartate sensor was normal and not mutant. That was the key evidence suggesting that the food sensors -- even those that detect different kinds of food -- "normally work not as individuals, but in teams," Parkinson said.

"If one of them is on the disabled list and there's no replacement, the team is short-handed and it won't work properly," he added.

In an accompanying commentary in PNAS, Joseph Falke of the University of Colorado at Boulder discusses how teams of chemical sensors or receptors might amplify a faint food-chemical signal so a bacterium swims toward food. While only one of three receptors in a team might detect the food chemical, all three sensors might send a signal because they touch each other.

But that would explain only a tripling of the strength of the signal, not the much greater increase discovered in earlier research.

As a result, Parkinson's team and Falke hypothesize that many teams of three sensors each might work together to form a league of chemical sensors capable of greatly amplifying a faint whiff of food into a strong signal that makes the bacterium swim toward its meal.

"One member of the team senses a chemical change, and the entire three-member team somehow sends an amplified signal," Parkinson said. "Neighboring teams in the cluster -- by a mechanism not understood -- become aware of that signal and join in. We call the cluster the league -- the league of teams."

Parkinson and Ames, a research associate, conducted the study with laboratory technician Rebecca Reiser and with Claudia Studdert, an Argentina National University biologist who spent 2001 on sabbatical at the University of Utah. - By Lee Siegel


[Contact: John S. Parkinson, Peter Ames, Remi Barron, Lee Siegel]

30-Apr-2002