Plant research opening doors to new antibiotics

9/4/2012

Dr. Katayoon Dehesh, Professor of Plant Biology in the UC Davis College of Biological Sciences, and her research team have recently made a groundbreaking discovery in plants that could ultimately transcend species and lead to the creation of novel new human antibiotics.

Her research focuses on the idea that when a plant cell experiences stress—whether from wounding, infection, or exposure to high light levels—the nucleus, home to the majority of the cell’s genetic material, activates genes necessary for coping with the stress.

But how does the nucleus learn that stress has occurred?

Dehesh’s team has discovered that chloroplasts—one of the organelles inside the cell that function as its sensors—actually send alerts to the nucleus in a process called retrograde signaling. Their research has shown, for the first time, that a small metabolite called Methylerythritol cyclodiphosphate (MEcPP) is produced in response to stress and sent to the nucleus via a specific pathway.

When MEcPP is received by the nucleus, it triggers activation of the gene hydroperoxide lyase (HPL). This gene is responsible for production of a range of metabolites that help a plant heal from or compensate for stress factors.

The significance of this discovery is two-fold. Primarily, this the first study to definitively prove that chloroplasts send stress signals to the nuclei. And second, what is happening in plants also occurs in bacteria.

Chloroplasts are thought to have originated from cyanobacterial ancestors through endosymbiosis: the process of free-living bacteria being taken inside another cell in a symbiotic relationship. Basically, one bacterial organism, with its own DNA and structure, swallows another bacterial organism, also with its own DNA and structure, and they exist happily together.

Over time, the bacteria that was swallowed evolved into what we see today as a chloroplast. Mitochondria, the chloroplast’s counterpart found in the cells of eukaryotic species, such as humans, are thought to have been formed in the same manner from proteobacteria.

“Within the plant community it has been always a question of how the organisms such as chloroplasts and mitochondria—which are really the bacteria captured by other bacteria—convey messages to the nucleus,” Dehesh says. “Our research has revealed not only the specific chemical, MEcPP, that is part of this process, but also the fact that this signal is not only happening within the plant cell, but also within the bacteria itself. It is deeply conserved.”

The benefit that this discovery could have for humankind is already apparent.

Previous research on the infectious process of chlamydia has shown that the presence of MEcPP is absolutely essential for the bacteria to successfully infect an organism. In its absence, infection simply does not occur.

But why?

Cell nuclei contain chromatin structures, DNA wrapped by proteins called histones. For genes to be transcribed, the histones must open up, allowing access to the DNA.
Dehesh believes that MEcPP somehow goes to the nucleus of an infected cell and modifies some of the DNA-histone interactions, opening up the chromatin in a very selective, targeted manner to allow expression of a selected group of genes.

In the case of chlamydia, when MEcPP is absent, there is no change in the DNA-histone structure and therefore no division of the infected cell.

“If MEcPP is not there, you can’t infect a person,” Dehesh says. “This could be a target for development of novel antibiotics.”

Further research will focus on understanding the mechanism and mode of action of MEcPP—how it changes the dynamics of the chromatin structure and functionality to allow expression of these genes.

Dehesh, who holds the Paul K. and Ruth R. Stumpf Endowed Professor of Plant Biochemistry, is also busy with two other ongoing research projects: first, developing a method for high-volume biofuel production by developing oil in plant leaves rather than seeds, and second, identifying stress-responsive DNA activity shared by yeast and plants.

One of Dehesh’s primary goals as the Stumpf endowed professor is to strengthen UC Davis’ research program by increasing student involvement and improving its relevance to human life. “Society should point the direction and research should follow so that it is from the people back to the people,” she says.

One might think that is a heavy research load to carry, but Dehesh doesn’t feel the weight. “I don’t know if it feels like work, but I have a lot of fun,” she says.