UNMC researcher finds ‘death pathway’ in bacteria

Vinai Thomas, PhD

Vinai Thomas, PhD

A new study by researchers at the University of Nebraska Medical Center has uncovered a "death pathway" among bacteria, a mechanism that authors suggest might be exploited as a therapeutic target against infectious diseases.

Vinai Thomas, PhD, an associate professor in the UNMC Department of Pathology and Microbiology, is the senior author of the study, published in the journal PNAS (Proceedings of the National Academy of Sciences) in November.

"If such a pathway exists in bacteria, you could design compounds that activate it, that influence a pathogen to kill itself," he said. "There are compounds in nature, such as acyldepsipeptide, that could potentially activate this mechanism and cause bacteria to self-digest and die."

He suggested that the death mechanism – sparked by a protease called ClpP – may be an attempt to ensure the survival of other sibling bacteria.

"When damaged cells in a population die, the remaining healthier populace has a better chance of competing in environments where the conditions favor growth," Dr. Thomas said. "Thus, the activation of cell death in damaged cells preserves the whole population's fitness and reproductive potential under stress."

Bacteria, he noted, have traditionally been considered "immortal," since they can continuously keep dividing if food is provided and toxic waste byproducts are removed.

"They don’t technically have a programmed pathway to die like human cells do," he said.

At least, that’s been the thought so far.

But the PNAS study suggests this is not always the case. "If bacteria undergo extensive damage with respect to the proteins they have, they appear to ‘commit suicide,’ " Dr. Thomas said. "If resources are limited, death would be a way to make sure that the healthiest population gets the resources it needs."

In a commentary written about the study in PNAS, author Anupama Khare, PhD, of the National Institutes of Health, said the study opens several avenues of further inquiry. Dr. Thomas said that understanding what the ClpP protease targets may better enable clinicians to make therapeutic use of the "death pathway."

"We know that this ClpP protease is very important to this process," Dr. Thomas said. "The ClpP protease, with its accessory proteins, is an ATP-powered machine in the cell that can chew up damaged or unwanted proteins and route them for recycling. Thus, it functions as a protein quality control machinery. In addition, bacteria can divide rapidly to dilute out damaged proteins."

But its role in the death mechanism is less clear, Dr. Thomas said, and that is the next question the lab hopes to answer.

"What proteins ClpP targets in the cell to trigger cell death is much less clear. We describe one, but I’m sure there are others that need to be degraded to cause the cell to die. So that’s our next step – what are the targets of this protease?"

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