In the Oct. 26, 2007, issue of Science, researchers reported a finding that may provide the template for a new class of antibiotics: using a secreted peptide, E. coli bacteria, which apparently can talk each other into suicide via quorum sensing.

In multicellular life forms, programmed cell death or apoptosis is a basic mechanism for keeping cells in line with the needs of their parent organism. And despite their ability to survive and replicate on their own, bacteria, too, in many ways act more like multicellular organisms than free agents.

Hanna Engelberg-Kulka has been studying the ways in which bacteria act like communities for decades. "It is my pride to be one of the first to look at bacterial cells . . . as a community," she told BioWorld Today. Engelberg-Kulka is professor of molecular biology at Hebrew University in Jerusalem and the senior author of the Science paper.

Bacterial communication via secreted factors, also known as quorum sensing, allows bacteria to sense their population density. Growth and virulence are among the long list of things that are influenced by quorum sensing, as is programmed cell death. As the authors explained in their paper, "when challenged by stressful conditions that trigger. . . cell death, the bacterial population can act like a multicellular organism in which a subpopulation of cells dies and releases nutrients and/or signaling molecules, and/or clears phages, thereby permitting the survival of the bacterial population as a whole."

But how bacteria talk each other into kicking the bucket remained unknown. In their Science paper, the researchers first showed that a quorum-sensing factor for suicide existed by taking the fluid from bacterial cultures with a high density and adding it to cultures with lower cell density. That treatment caused the known cell death mechanism in E. coli to kick in, in response to antibiotics, demonstrating that cell death required what the researchers called an "extracellular death factor" or EDF.

Characterizing the factor, though, turned out to be "very hard work - it took two years," Engelberg-Kulka said. The reason was that the factor being destroyed by the mass-spectrometry methods used to characterize it.

Specifically, it turned out that the peptide they were looking for was destroyed by the acidic conditions of normal mass spectrometry; once a method had been worked out to conduct mass spectrometry under conditions of neutral pH, the researchers were able to show that EDF was a linear, five-amino acid peptide containing four arginines and a central tryptophan.

A synthetic version of the peptide was able to restore cell death to low-density bacterial cultures. Further work showed that each of the amino acids is important for the peptide to function - which might not be so surprising. Engelberg-Kulka recalled discussing her results with a colleague who retorted that "with only five amino acids, each of them had better be important."

Engelberg-Kulka said that the technological advance that allowed them to characterize the peptide at less acidic pH values should "contribute to the identification of other peptides that are sensitive to normal mass spectrometry conditions."

She was circumspect when asked about the potential of her team's discovery to be used therapeutically. Her team is working both on finding similar peptides in other bacterial strains, and testing, with collaborators, whether EDF has antibacterial activity in animal models. But she noted that "I can't say we have an antibiotic."

The work is in its very early stages, and among many other things that can stymie drug development, the peptide or any analogue might be degraded and turn out to be ineffective therapeutically.

But if it does pan out, she noted, the finding could provide the basis of a new class of antibiotics. In that case, this class has one advantage over many other classes built in. Most antibiotics act on intracellular targets, and so need to be designed to both be able to enter cells and affect their targets when they do. But for a quorum-sensing mechanism, the first problem presumably would be taken care of already. "It enters the cell anyway - that's the way it is working naturally."