‘How Bacteria Sense and Remember’ – Distinguished Faculty Address

PULLMAN, Wash. — If you want to answer the big questions in life, you’ve got to think small. That’s one reason why scientist Gerald L. Hazelbauer works with the bacterium E. coli.
The Washington State University professor and chairman of biochemistry/biophysics has been selected to deliver WSU’s 65th Distinguished Faculty Address Thursday, Feb. 25 at 7:30 p.m. in the Webster Physical Sciences Building, Room 16. The address series, designed for an all-university audience, dates back to 1958 and carries a $2,500 prize. His talk is titled “Knowing Where You Are and Where You’ve Been: How Bacteria Sense and Remember.”
Hazelbauer’s work with E. coli began in the 1960s when he was a graduate student in the lab of Julius Adler at the University of Wisconsin. Adler had been fascinated since childhood with the question of how organisms sense and respond to their environment. As a scientist, he looked for and found a system that would lend itself to the molecular study of the question. He found it in chemotaxis by E. coli, a behavior in which these bacteria sense small molecules in their external environment and move in response to them.
Scientists had already shown that bacteria can be attracted to a favorable chemical environment such as one containing the sugar galactose. Conventional wisdom said that bacteria were attracted as a result of using the galactose, breaking it down for food or energy. Adler, however, suspected that bacteria sensed the galactose by recognizing it rather than by using it. He also realized that he could test his hypothesis with the newly developing tools of molecular biology.
Adler reasoned that if the bacteria recognize galactose, then there must be something on the bacteria’s surface that does that recognizing, something that today we’d call a receptor. He further reasoned that it most probably was a protein, and he told Hazelbauer, “If you can find that protein, you can get a Ph.D.”
Hazelbauer did.
Research has shown that the E. coli chemotaxis receptor for galactose is actually a complex of three parts. On the outside of the bacteria is a section that recognizes galactose, the section Hazelbauer identified as his thesis project. A second section is on the inside of the bacteria, and these two sections are connected by a third section that was also discovered by Hazelbauer.
When the external section of the receptor recognizes and binds galactose, a signal passes through the entire receptor and causes sequential changes in two proteins inside the bacteria. The second of these proteins interacts with the gear shift on the flagella’s rotary motor and suppresses its tumbling so that the bacteria swims smoothly in the direction of the galactose. Normal movement for E. coli consists of “runs” and “tumbles,” which propel the bacterium aimlessly.
Many species other than bacteria use a similar two-protein sensing system, says Hazelbauer. “Two- thirds of all life on earth use it.” One place the system has not been found to date is in animals. This makes it of interest for those developing antibiotic drugs that kill bacteria without harming the patient.
Since he identified the connecting section of the receptor, Hazelbauer has concentrated on learning how the receptor works. “And I’m still trying to figure that out,” he says.
Hazelbauer discovered that the receptor section inside the bacteria contains a number of separate sites that are modified when the bacteria adapts to a continuing stimuli. He determined the three-dimensional structure of the receptor’s connecting section. His work is now focused on determining how the individual parts of that section move with respect to each other. This movement signals the bacteria that galactose is present around it.
E. coli use their galactose receptors to determine whether the surrounding concentration of galactose is changing. They can do so because the binding of galactose to the receptor causes more than a change in flagellar rotation. It also causes, although more slowly, modifications to sites on the inside section of the receptor.
It appears that bacteria periodically monitor the modification sites and galactose binding. The modification sites tell the bacteria about the concentration of galactose some few seconds in the past. The galactose binding tells it about the current concentration. If the two differ, then the concentration is changing.
When the concentrations are changing, the bacterium will send a signal to the flagella’s gear shift and the bacterium’s movement will be adjusted. If the concentrations are the same, however, no adjustments are necessary and no signals are sent. The bacterium is adapted to its surroundings and doesn’t need to change its movement.
Just as E. coli adapts to its surroundings, we adapt, for like E. coli’s sensory systems, ours are designed to detect change. If we walk into a room with a bad smell, for example, we notice it. If we remain in the room for several minutes, we notice it much less or not at all.
Current evidence suggests that, at the molecular level, our adaptation may not be all that different from that of E. coli. Proteins in nerves are modified in the course of adaptation in a way that is analogous to the galactose receptor. “These changes in proteins appear to be a first step or at least a part of the first step of our storing information,” says Hazelbauer. We, again like E. coli, have a memory.
Much progress has been made since the 1960s in learning about how organisms sense their environments. “We set out then to study a fundamental issue in biology with the newest and most powerful of molecular tools,” says Hazelbauer. “These tools have made molecular biology one of the great intellectual success stories of the second half of the twentieth century. We’ve been able to learn a great deal about how life works at the level of the molecules.”