Assistant Professor of Biochemistry
Franklin Wayne Outten | University of South Carolina, Columbia
The Iron Man
Where some see rust as the unfortunate sign of corrosion, Wayne Outten catches a glimpse of the primordial days of life.
Rust, for him, is a reminder that iron's ability to exchange atoms and form oxides, along with its abundance, made it a key element in all biological systems early in evolutionary history. That has led to an intracellular arms war over iron, with survival at stake.
At the University of South Carolina, Outten is exploring the basic science of how pathogens - like E. coli and ones that cause TB and malaria - survive when they face what he calls iron starvation. And with that insight, industry might one day come up with new antibiotics to knock out those pathogens.
Iron has a special character. Its atomic patterns make it one of the so-called transition metals - falling between two main groups of elements in the periodic table. Iron's give and take of electrons made it ideal for nature to use in biochemical reactions like respiration, photosynthesis and conversion of nitrogen, to, say, ammonia, or nitrogen fixation.
"But there's a catch," Outten said. Cells need iron in a soluble form, and in nature iron tends to lazily settle into a state with oxygen that forms insoluble compounds. So iron plays hard to get. In the human body, though, it's easier for those pathogens.
"The typical human has large amounts of iron circulating in the body as the heme part of the oxygen-carrying protein hemoglobin, providing a virtual buffet for the bacteria," Outten said.
In turn, the body has found ways to make its iron harder to get at. During infection, the body sequesters iron, lowering the amount in circulation to starve the infecting bacteria of this key nutrient.
Our immune system aggressively targets iron-containing proteins by dousing the bacteria in large amounts of highly oxidizing molecules, generated from oxygen and nitric oxide. Those oxidants exploit the sensitivity of iron to donate electrons, and in the process set up damage to the iron-containing proteins in the bacteria.
"It's a two-pronged attack," said Outten, who, if you haven't guessed, was in the U.S. Army Reserve for 14 years. His study of iron and bacteria began in postdoctoral work at the National Institutes of Health.
Those bacteria are being starved for available iron as their own personal stores of iron proteins are targeted by the human immune system.
"But bacteria are a wily foe," he said. They have developed iron acquisition systems that seek out iron in human hemoglobin and elsewhere. They try to evade or neutralize the reactive oxygen and nitrogen molecules that target their iron.
In this biological arms race, some bacteria have acquired a set of genes that allow them to maintain a critical iron supply, using molecules with iron and sulfur, thus the name Fe-S cluster. It helps them stave off iron starvation and oxidative stress.
Attack those genes, collectively known as the Suf (sulfur formation) pathway in bacteria, with antibiotics and you could knock out the pathogens' survival kit.
"We are somewhat akin to a 2-year-old building a tower of blocks in our ultimate goal," Outten says. "Once we build up all of this knowledge about the Suf pathway, we are just going to use it to gleefully knock the whole system down."
But first, Outten and his lab must solve all that inorganic chemistry.
Education Component
Outten plans outreach efforts to increase the numbers of African-American students in South Carolina who go to graduate school. He will create an undergraduate summer research program to recruit students in the Columbia, S.C., area.
Outten, who sometimes bring his toddler, Lyla, and her older brother, Bryce, into his lab during discussions of Suf pathways, puts strong emphasis on undergraduate education. One student in his lab won the award for outstanding undergraduate research at a South Carolina Academy of Sciences meeting, and received a Howard Hughes Undergraduate Research Scholarship.
Outten's wife, Caryn, is also a researcher at South Carolina, working on how humans respond to oxidative stress.
