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Science Forum Index » Medicine Forum » How Tuberculosis Steals Iron...
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| ironjustice at (no spam) aol.com... |
 Posted: Fri Aug 01, 2008 3:36 am |
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How Some Bacteria May Steal Iron From Their Human Hosts Discovered By
Syracuse University Scientists
Article Date: 01 Aug 2008 - 4:00 PDT
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 its
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 is not an 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."
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Article adapted by Medical News Today from original press release.
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Source: Sara Miller
Syracuse University
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