Like their human hosts, bacteria need iron to survive and they must obtain that iron
from the environment. While humans obtain iron primarily through the food they
eat, bacteria have evolved complex and diverse mechanisms to allow them access to
iron. A Syracuse University research team led by Robert Doyle, assistant professor of
chemistry in The College of Arts and Sciences, discovered that some bacteria are
equipped with a gene that enables them to harvest iron from their environment or
human host in a unique and energy efficient manner. Doyle's discovery could
provide researchers with new ways to target such diseases as tuberculosis. The
research will be published in the August issue (volume 190, issue 16) of the prestigious
Journal of Bacteriology, published by the American Society for Microbiology.
"Iron is the single most important micronutrient bacteria need to survive," Doyle
says. "Understanding how these bacteria thrive within us is a critical element of
learning how to defeat them."
Doyle's research group studied Streptomyces coelicolor, a Gram-positive bacteria that
is closely related to the bacteria that causes tuberculosis. Streptomyces is abundant in
soil and in decaying vegetation but does not affect humans. The TB bacteria and
Streptomyces are both part of a family of bacteria called Actinomycetes. These
bacteria have a unique defense mechanism that enables them to produce chemicals to
destroy their enemies. Some of these chemicals are used to make antibiotics and other
drugs.
Actinomycetes need lots of iron to wage chemical warfare on their enemies; however,
iron is not easily accessible in the environments in which the bacteria live-e.g.
human or soil. Some iron available in the soil is bonded to citrate, making a
compound called iron-citrate. Citrate is a substance that cells can use as a source of
energy. Doyle and his research team wondered if the compound iron-citrate could be
a source of iron for the bacteria. In a series of experiments that took place over more
than two years, the researchers observed that Streptomyces could ingest iron-citrate,
metabolize the iron, and use the citrate as a free source of energy. Other experiments
demonstrated that the bacteria ignored citrate when it was not bonded to iron;
likewise, the bacteria ignored citrate when it was bonded to other metals, such as
magnesium, nickel and cobalt.
The next task was to uncover the mechanism that triggered the bacteria to ingest
iron-citrate. Computer modeling predicted that a single Streptomyces gene enabled
the bacteria to identify and ingest iron-citrate. The researchers isolated the gene and
added it to E. coli bacteria (which are not Actinomycete bacteria). They found that
the mutant E. coli bacteria could also ingest iron-citrate. Without the gene, E. coli
could not gain access to the iron.
"It's amazing that the bacteria could learn to extract iron from their environment in
this way," Doyle says. "We went into these experiments with no idea that this
mechanism existed. But then, bacteria have to be creative to survive in some very
hostile environments. And they've had maybe 3.5 billion years to figure it out."
The Streptomyces gene enables the bacteria to passively diffuse iron-citrate across the
cell membrane, which means that the bacteria do not expend additional energy to
ingest the iron. Once in the cell, the bacteria metabolize the iron and, as an added
bonus, use the citrate as an energy source. Doyle's team is the first to identify this
mechanism in a bacteria belonging to the Actinomycete family. The team plans
further experiments to confirm that the gene performs the same signaling function in
tuberculosis bacteria. If so, the mechanism could potentially be exploited in the fight
against tuberculosis.
"TB bacteria have access to an abundant supply of iron-citrate flowing through the
lungs in the blood," Doyle says. "Finding a way to sneak iron from humans at no
energy cost to the bacteria is as good as it gets. Our discovery may enable others to
figure out a way to limit TB's access to iron-citrate, making the bacteria more
vulnerable to drug treatment."
