Bacteria Suicide Mechanism Might Lead to New Drugs

Researchers from the Hebrew University of Jerusalem discovered a new bacterial communication factor that is associated with bacteria’s death. The intestinal bacteria E. coli activate a “suicide” system in response to stressful conditions and to the density of their population. The newly dicovered designated Extra-cellular Death Factor (EDF) enables the bacteria to monitor their surroundings and commit suicide when necessary. As other bacteria also employ similar systems, the new discovery may have significant consequences leading to the development of a new class of antibiotics.
 Professor Hanna Engelberg-Kulka (Credit: Hebrew University-Hadassah Medical School)
Professor Hanna Engelberg-Kulka
(Credit: Hebrew University-Hadassah
Medical School)

A group of Hebrew University scientists headed by Prof. Hanna Engelberg-Kulka of the Department of Molecular Biology at the Hebrew University – Hadassah Medical School have discovered a new bacterial communication factor. The researchers revealed the discovery of the extra-cellular death factor, and described some of its characteristics and several genes that are involved in its generation in an article published in the October 2007 issue of Science magazine. 

The new factor is produced and secreted by the intestinal bacteria Escherichia coli. This factor serves as a communication signal between single bacterial cells and enables the activation of a “suicide module” which is located on the bacterial chromosome and is responsible for bacterial cell death under stressful conditions. 

The “suicide module” is a toxin-antitoxin module located on many bacterial chromosomes, including those of pathogens. It enables intracellular expression of a stable toxin and of an unstable antitoxin that counteracts the action of the toxin. Any stressful condition that prevents the module’s expression in E. coli may lead to a reduction of the antitoxin’s levels in the cell, permitting the toxin to act and kill the cell. 

This system of programmed cell death (PCD) in E. coli is also dependent on the density of the bacterial population. Bacteria communicate with one another, monitor each other’s presence and modulate gene expression in response to population density via a variety of quorum-sensing signal molecules. The novel peptide (a very short protein chain) discovered by the Hebrew University researchers is the quorum-sensing molecule secreted by E. coli and which activates the bacteria’s death system. Therefore, this molecule has been designated EDF (Extra-cellular Death Factor).  

While suicidal cell death is counterproductive for the individual bacterial cell, it may benefit the bacterial community under stressful conditions. Under such conditions, a major sub-population within the bacterial culture is signaled by EDF and subsequently dies. The dying cells clear phages and/or release nutrients and/or signal molecules, permitting the survival of the population as a whole.  

Illustration of the effects of EDF (Credit: Hebrew University) 
Illustration of the effects of EDF
(Credit: Hebrew University)

Understanding how the EDF functions together with the ability to chemically synthesize an identical peptide carrying EDF activity may provide a basis for a new class of antibiotics. Such drugs may specifically trigger bacterial cell death in E. coli and probably in many other bacteria, including those pathogens that also carry the “suicide module”. Drugs of this type may become incredibly important given the growing resistance of bacteria to existing antibiotics. 

TFOT previously covered a couple of related issues. The first is an approach for fighting bacterial transfer of information and resistance to antibiotics, devised in the University of North Carolina. The other is a method for attacking biofilm, another consequence of bacterial quorum-sensing, developed by the Harvard-MIT Division of Health Science and Technology researchers. 

More information on the Hebrew University of Jerusalem study can be found on the university’s website.

Further discussion of the discovery of the E. coli Extra-cellular Death Factor can be found in the TFOT forums.