The U.S. Department of Energy has awarded a $1.8 million grant to a team headed by Anne Summers, a UGA microbiologist, to examine what happens to proteins when living cells are exposed to mercury.
“The practical application of this project is to identify especially vulnerable and slowly repaired proteins as biomarkers for detecting the most subtle mercury damage long before it could be manifested by more obvious changes, such as delayed cell division or the formation of mutations,” said Summers. “Although we will study these phenomena in bacteria, many potential target proteins in plants and animals have evolved from counterparts in bacteria.”
Others involved in the project are Susan Miller, a protein chemist at the University of California-San Francisco, and Mary Lipton, a biological mass spectrometrist at the Department of Energy Pacific Northwest National Laboratory.
There is increasing interest in the health effects of mercury. The versatile chemical properties of this silvery metal, known since antiquity and named for the messenger of the Roman gods, have led to its use in such diverse applications as cosmetics, antiseptics, metallurgical mixtures and industrial catalysts.
Although children once played freely with the fascinating shiny, heavy liquid released from broken glass thermometers and had their cuts and scrapes painted with a mercury-based treatment, such uses have been phased out as the environmental burden of this very mobile toxic element has become apparent.
Summers already studies how bacteria protect themselves from naturally occurring deposits of mercury ores such as those in southern Europe, northern Africa, China, Russia and western North America. Bacteria can convert the two most toxic forms of mercury into comparatively harmless (for bacteria) volatile mercurial vapor.
Understanding the resistance mechanism provided clues to why cells are vulnerable to mercury poisoning.
“Superficially, this seems obvious,” said Summers, “since mercury forms strong bonds with compounds that contain the element sulfur, and life’s chemistry uses many sulfur-containing compounds for everything from production of cellular energy to protection from radiation damage.”
The very abundant small sulfur compounds made by these ubiquitous cellular defense systems are, in principle, capable of “mopping up” mercury and flushing it out of the cell. The paradox of mercury poisoning is that cells can be damaged by mercury concentrations 1,000 times lower than the concentrations of their abundant natural defense molecules. It seems that some proteins bind mercury so tightly that these natural cellular compounds can’t remove it.
Seeing changes in a cell’s entire complement of proteins is only recently possible through a type of analysis called proteomics. Enabled by advances in mass spectrometry, this analysis reveals alterations in the protein of treated cells compared to its counterpart in untreated cells.
In previous work, Summers and her collaborators found that mass spectrometry can detect proteins with attached mercury atoms. They also have shown that one of the bacterial resistance proteins can pull mercury right off a poisoned cellular protein.
Now, they will look at the full array of proteins in the cell to find those readily modified at sub-lethal mercury concentrations, and, by tracking cells after exposure, they will see which proteins can be restored by basic cellular repair processes and how repair differs when the mercury resistance genes are present.