Study Finds Bacteria Evolve Rapidly to Adapt to Nutritional Availability

He was studying how bacteria finds and draws iron into itself when he made the startling discovery.

The National Institutes of Health has awarded O’Brian a four-year, $1.28 million grant to study the mechanisms of bacteria mutating to accept iron, and how the organism expels excess iron.

O’Brian’s discovery was made almost by accident, he says. The bacteria Bradyrhizobium japonicum was placed in a medium along with a synthetic compound to extract all the iron.

Having been deprived of the iron needed to multiply, O’Brian expected the bacteria to lie dormant. But to his surprise, the bacteria started multiplying.

“We had the DNA of the bacteria sequenced on campus, and we discovered they had mutated and were using the new compound to take iron in to grow,” he said. “It suggests that a single mutation can do that. So we tried it again with a natural iron-binding compound, and it did it again.”

The speed of the genetic mutations — 17 days — was astonishing.

“We usually think of evolution taking place over a long period of time, but we’re seeing evolution — at least as the ability to use an iron source that it couldn’t before — occurring as a single mutation in the cell that we never would have predicted,” O’Brian says.

“The machinery to take up iron is pretty complicated, so we would have thought many mutations would have been required for it to be taken up,” he says.

The evolution of the bacteria does not mean it is developing into some other type of entity. Evolution can also change existing species “to allow them to survive,” O’Brian notes.

Bacteria is the most abundant life form on the planet, having been around for 3 billion years, evolving and adapting. O’Brian says the significance of the discovery of near instantaneous evolution depends on a few factors.

“It will depend on how broadly applicable it is,” he says. “Can we characterize the mechanisms, and look around and see if they are in other systems? How does this affect bacterial communities? How important is it for human health?”

O’Brian says other researchers may take up work on how the new knowledge could impact human health.

For instance, patients receiving treatment for iron overload often develop bacterial infections. Knowing how bacteria adapt to iron in their environment could lead to improved methods of managing patient health, O’Brian notes.

The mutation may not be related to how bacteria become resistant to antibiotics. The mutation that O’Brian observed resulted in a “gain of function,” a much more complicated event than the adaptation to block an antibiotic, he says.

Organisms can adapt by switching genes on and off. Part of the grant is to study how bacteria expel excess iron by turning on different genes.

O’Brian is principal investigator on the grant titled “Bacterial Adaptation to Iron Stress.”

Its three specific aims are to:

• characterize the plasticity of outer membrane receptors to acquire gain-of-function mutations that allow rapid adaptation to available iron
• identify and characterize the periplasmic components of ferric siderophore uptake that allow rapid adaptation to available iron
• elucidate the mechanism of the iron exporter MbfA and characterize its functional relationship with the iron storage protein bacterioferritin

The work now is “strictly scientific,” but uses could be in the offing.

“There is the understanding of a mechanism that may help to better understand how you can approach an infectious disease, or approach remediation of the environment, using bacteria,” O’Brian says.

The grant will be administered through the National Institute of General Medical Sciences. Collaborators in O’Brian’s laboratory are:

• Anushila Chatterjee, graduate research assistant
• Thomas Hohle, PhD, postdoctoral research associate
• Alasteir Ong, graduate research assistant
  
• Fengyue Zhang, graduate research assistant

Chatterjee, Ong and Zhang are all students in the doctoral program in biochemistry.