Bacteria Banter

Many readers may remember ear infections as a constant problem of their youth. They would wake up and feel that familiar pain, and a visit to the doctor would provide them with only the added discomfort of having to either swallow or chew some revolting pills. Pill after pill, and the pain would subside, only to return again a few weeks later.

But after a while, the antibiotics would become ineffective, leaving the doctor no choice but to prescribe another medication — which, in turn, would eventually cease to bring results as well.

Is this a familiar scene? Probably so, but young children may soon not have any more to fear because of scientists like University molecular biology professor Bonnie Bassler.

Bassler has devoted the last 11 years of her professional life to the study of bacteria. More specifically, she has researched how bacteria interact, and has made the startling discovery that they actually communicate with each other in order to work as a team. Rather than exist separately as single-cell organisms, they communicate through the phenomenon known as quorom sensing to create a defensible community of cells.

Bassler said she is excited about her lab's findings. "It seemed like an incredibly interesting phenomenon that bacteria can talk to each other and coordinate the behavior of the whole community," she said. "It lets bacteria be multicellular, rather than act individually."

Bacteria are single-cell clones of each other. They grow and divide, doubling in number through each division, Bassler explained. Each bacterium secretes molecules like hormones, and each has detectors on the cell's surface for those hormones.

"If there are enough of them, the local signal grows so they can detect it and can respond by turning on genes, like for light," she said.

She added however that these bacteria can detect the hormone only when it reaches a certain level.

"It's all or nothing," Bassler said. "Below the threshold, they don't do anything — at or above the threshold they act."

Bassler said this type of communication was discovered through the study of bioluminescence of bacteria in oceans. As the bacteria detect the presence of their species, they work collectively to create light.

The implications of Bassler's research are staggering. By learning more about quorom sensing, she has also found that this method of communication helps pathogens — bacteria that are harmful to the host — control their virulence.

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Bassler is quick to point out that most bacteria are not harmful to other organisms and that humans breathe in millions of bacteria every day. Rather, the type of bacteria she works on are pathogenic, like E. coli, which are harmful to humans.

Bacteria such as E. coli and salmonella, as well as those that cause staph and strep infections have been shown in several tests to "use quorom sensing to regulate virulence," Bassler said.

"There is increasing evidence that in many bacteria, virulence is regulated by quorom sensing," she said "If you could design drugs that screwed up the bacteria's ability to count themselves, then they wouldn't turn on virulence."

She said there is a great need for new drugs such as these, given the growing number of drug-resistant strains of pathogenic bacteria. She added that drugs that could interfere with quorom sensing would signal a momentous step forward in the pharmaceutical business, but that they won't cure all the "ills" of society.

"I hope it works on a lot of bacteria," Bassler said. However, she added that some pathogens do not regulate virulence through quorom sensing. She said that any drug created by using her research is "not going to cure every disease. It can't be the total wonder drug."

Bassler is working with California-based Quorex Pharmaceuticals to create these drugs. Jeffrey Stein, Chief Scientific Officer of Quorex said a drug that would target quorom sensing "really has the potential to represent a new approach to antibiotics."

He said this method of attacking pathogenic bacteria is "smarter" because it reduces the risks of creating drug-resistant bacteria.

"We're not killing them directly, but rather indirectly," he said. "We're shutting off their ability to communicate and survive in the host."

He added that as a result, these bacteria would not be able to work together to feed off the host and would weaken and eventually be killed by the host's immune system.

"It's analogous to modern warfare. You shut down the communication system, and with it, their ability to make an offensive attack," Stein said.

He said there is a great need for drugs like these because today's antibiotics have been over-prescribed. "When they're applied for viral infections, it provides ample opportunities for bacteria to become resistant to the drug," Stein pointed out. "When most microbes are killed, some survive, leading the next generation of genes to be resistant to the drug."

He added that virtually every antibiotic on the market has a population of bacteria that is developing a resistance to it.

Stein said his company has been able to make progress because of the bioluminescence that Bassler originally studied. He said his company uses bioluminescent bacteria as a screening tool to discover drugs to interfere with the communication pathway used in quorom sensing.

"These bacteria all produce a common molecule called an auto-inducer molecule," he said.

"Our task is to use that molecule as a basis for drug design," Stein said. "We're designing analog compounds that interfere with the ability of the pathogen to recognize the natural molecule," thus shutting down quorom sensing.

Stein said he hopes to see Bassler's research come to fruition in the form of a drug in the near future. He estimated that Quorex will have several drug candidates ready for the Food and Drug Administration's initial trials in the next three years.

He added that if a drug passes the three stages of FDA testing, the public could possibly use the drugs before the end of the decade. He said however, that it could be even sooner because the FDA has been known to expedite testing of "anti-infectors" in times of severe need.

"For me, I'm always marveling at how amazing bacteria are. They are incredibly sophisticated," Bassler noted. "For example, these bacteria make multiple types of these hormones to detect their own species and other species. They can tell apart different types of bacteria."

She added that she and the rest of her lab never predicted they would find bacteria to be so complex. She admitted, "I always guess it's simpler than it is."

Bassler said she is pleased with the results she and her team have found. She added she is also excited to see the development of drugs using her research.

"Eleven years ago, I didn't imagine this," she said. "To think about the application of my research is incredible."

She also said that the possibilities of the developments as a result of her work are "beyond my dreams — I didn't dare dream these things a decade ago."

She said she also gets a feeling of satisfaction knowing that her research may save lives, if the Quorex-made drugs survive FDA tests. "You go into this field wanting to help people, but chances are slim that you're going to," Bassler said.

For now the public will have to wait and see. Bassler will continue researching the intricacies of quorom sensing, while Quorex will try to apply Bassler's findings to its existing pool of knowledge in search of the perfect drug. With Bassler's research and Quorex's manpower and financial resources — at the time of publication, Stein was on the East Coast meeting with investors in an effort to raise a second round of financing to add to the company's previously raised $2.2 million — that drug may actually become a reality.

For millions of Americans who suffer from ear infections, strep throat, salmonella poisoning and other pathogen-related illnesses each year, Bassler and Quorex provide a glimmer of hope. And given recent reports about the existence of new forms of drug-resistant Tuberculosis — another pathogen that uses quorom sensing to regulate virulence — as well as severe E. coli breakouts at restaurants like Jack-in-the-Box, a bacteria fooler like the one Bassler envisions is just what the doctor ordered.