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Anthrax / iron
Anthrax / iron
Source: University of California - Berkeley
Date: December 8, 2006
New Finding Points Way To Foiling Anthrax's Tricks
University of California, Berkeley, chemists have discovered a trick
that anthrax bacteria use to make an end run around the body's
defenses, but which may turn out to be their Achilles' heel.
Anthrax bacteria (green) secrete two iron-scavenging molecules, the
siderophores bacillibactin and petrobactin, represented by
ball-and-stick structures with a red iron atom inside. One of these,
bacillibactin (top right), is intercepted by the protein siderocalin
(blue) produced by the human immune system, but the second, petrobactin
(lower left), slips through the body's defenses.
The UC Berkeley scientists, working with colleagues at the University
of Mississippi Medical Center in Jackson and the Fred Hutchinson Cancer
Research Center in Seattle, uncovered the trick while studying how
these deadly bacteria steal iron from their human hosts to grow and
reproduce.
"Humans make a protein called siderocalin to defend against bacteria in
the continual arms race between pathogen and host. This is the first
example of a protein produced by the human immune system that disrupts
bacteria's iron scavenging system," said Ken Raymond, UC Berkeley
professor of chemistry and faculty scientist at Lawrence Berkeley
National Laboratory.
Anthrax bacteria are known to produce two small molecules -
bacillibactin and petrobactin - that snatch iron away from the human
body's iron transporter molecules, called transferrin. These
scavengers, or "siderophores," are essential to anthrax's ability to
grow rapidly, especially after the spores are inhaled, though why the
bacteria need two siderophores to do the job has been an enigma.
The new study shows why anthrax bacteria require two siderophores
working by two different mechanisms. Siderocalin, the human immune
protein, binds bacillibactin and effectively sidelines it, the
researchers found. Apparently, anthrax fielded a second "stealth" iron
scavenger, petrobactin, to get around the human defense against the
first scavenger. Petrobactin is not bound by siderocalin.
As far as is known, the human immune system has yet to launch a
successful counterattack against the stealth siderophore, but that
doesn't mean humans can't design one of their own, according to
Raymond. His UC Berkeley team and the Seattle team are now exploring
how their discovery could be used to diagnose or treat anthrax.
The researchers published their findings Nov. 28 in the online edition
of the Proceedings of the National Academy of Sciences. Their paper
will appear in the Dec. 5 print edition.
Many bacteria, including the benign Escherichia coli in our gut, make
small molecules called siderophores that snatch iron from the tissues
of their host so that the bacteria can reproduce. Some strains of E.
coli produce more than one kind of siderophore, apparently attacking on
several fronts to get the iron they need.
The discovery of a similar strategy in anthrax, Bacillus anthracis,
suggests that producing more than one siderophore is a general strategy
of bad as well as benign bacteria, according to the researchers. To
date, however, only the pathogenic forms of E. coli and Bacillus have
been found to produce a siderophore not bound by siderocalin; the
non-pathogenic forms that produce more than one siderophore base them
on the same molecular structure to which siderocalin binds.
Anthrax is a potential bioweapon because it is nearly always fatal when
inhaled. Its long-lived spores grow rapidly in the lungs, leading to
breathing problems and shock within days. While a vaccine is available,
there is no effective treatment.
The bacteria succeed by forming capsules that invade lung cells, then
capturing iron in order to reproduce, and finally, manufacturing a
toxin that kills the cells and releases thousands of new spores into
the bloodstream.
Because the iron-capture stage is critical to growth, it has become a
recent focus of attention as a possible drug target. Raymond, who has
studied bacterial siderophores that capture iron for 35 years, recently
teamed up with Roland Strong of the Seattle cancer center to study
siderocalin, a human protein Strong had found that appeared to
interfere with the siderophores secreted by anthrax bacteria.
To study the role of this protein, Raymond and UC Berkeley graduate
students Rebecca J. Abergel and Trisha M. Hoette approached an anthrax
research laboratory run by B. Rowe Byers, professor of microbiology at
the University of Mississippi Medical Center, to obtain samples of
anthrax siderophores. Because bacteria secrete siderophores, these
molecules can be separated from the bacteria and studied without danger
of infection.
Using these anthrax bacteria extracts, Abergel and Hoette isolated the
two siderophores, bacillibactin and petrobactin, and showed that
siderocalin tightly binds bacillibactin, preventing it from capturing
iron from human cells. However, siderocalin does not prevent
petrobactin from binding iron.
Interestingly, bacillibactin is very similar to siderophores in other
bacteria, including enterobactin, which is produced by several
pathogenic bacteria that live in the gut, such as Salmonella enterica
and pathogenic strains of E. coli. These two bacteria also contain a
second siderophore, aerobactin, with a molecular structure similar to
petrobactin.
The researchers suggest that producing a second, stealth siderophore -
petrobactin or aerobactin - that has a different molecular structure
than bacillibactin and enterobactin may be a common response by
bacteria to the human body's production of siderocalin.
The research could lead to anti-anthrax drugs that target petrobactin
synthesis or iron-uptake, or to anthrax sensors that detect
petrobactin, which is not known to occur in any other pathogenic
bacteria.
The research was funded by the National Institutes of Health
* w w w .sciencedaily . com /releases/2006/11/061130191058.htm
Who loves ya.
Tom
Jesus Was A Vegetarian!
* jesuswasavegetarian.7h . com
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
Source: University of California - Berkeley
Date: December 8, 2006
New Finding Points Way To Foiling Anthrax's Tricks
University of California, Berkeley, chemists have discovered a trick
that anthrax bacteria use to make an end run around the body's
defenses, but which may turn out to be their Achilles' heel.
Anthrax bacteria (green) secrete two iron-scavenging molecules, the
siderophores bacillibactin and petrobactin, represented by
ball-and-stick structures with a red iron atom inside. One of these,
bacillibactin (top right), is intercepted by the protein siderocalin
(blue) produced by the human immune system, but the second, petrobactin
(lower left), slips through the body's defenses.
The UC Berkeley scientists, working with colleagues at the University
of Mississippi Medical Center in Jackson and the Fred Hutchinson Cancer
Research Center in Seattle, uncovered the trick while studying how
these deadly bacteria steal iron from their human hosts to grow and
reproduce.
"Humans make a protein called siderocalin to defend against bacteria in
the continual arms race between pathogen and host. This is the first
example of a protein produced by the human immune system that disrupts
bacteria's iron scavenging system," said Ken Raymond, UC Berkeley
professor of chemistry and faculty scientist at Lawrence Berkeley
National Laboratory.
Anthrax bacteria are known to produce two small molecules -
bacillibactin and petrobactin - that snatch iron away from the human
body's iron transporter molecules, called transferrin. These
scavengers, or "siderophores," are essential to anthrax's ability to
grow rapidly, especially after the spores are inhaled, though why the
bacteria need two siderophores to do the job has been an enigma.
The new study shows why anthrax bacteria require two siderophores
working by two different mechanisms. Siderocalin, the human immune
protein, binds bacillibactin and effectively sidelines it, the
researchers found. Apparently, anthrax fielded a second "stealth" iron
scavenger, petrobactin, to get around the human defense against the
first scavenger. Petrobactin is not bound by siderocalin.
As far as is known, the human immune system has yet to launch a
successful counterattack against the stealth siderophore, but that
doesn't mean humans can't design one of their own, according to
Raymond. His UC Berkeley team and the Seattle team are now exploring
how their discovery could be used to diagnose or treat anthrax.
The researchers published their findings Nov. 28 in the online edition
of the Proceedings of the National Academy of Sciences. Their paper
will appear in the Dec. 5 print edition.
Many bacteria, including the benign Escherichia coli in our gut, make
small molecules called siderophores that snatch iron from the tissues
of their host so that the bacteria can reproduce. Some strains of E.
coli produce more than one kind of siderophore, apparently attacking on
several fronts to get the iron they need.
The discovery of a similar strategy in anthrax, Bacillus anthracis,
suggests that producing more than one siderophore is a general strategy
of bad as well as benign bacteria, according to the researchers. To
date, however, only the pathogenic forms of E. coli and Bacillus have
been found to produce a siderophore not bound by siderocalin; the
non-pathogenic forms that produce more than one siderophore base them
on the same molecular structure to which siderocalin binds.
Anthrax is a potential bioweapon because it is nearly always fatal when
inhaled. Its long-lived spores grow rapidly in the lungs, leading to
breathing problems and shock within days. While a vaccine is available,
there is no effective treatment.
The bacteria succeed by forming capsules that invade lung cells, then
capturing iron in order to reproduce, and finally, manufacturing a
toxin that kills the cells and releases thousands of new spores into
the bloodstream.
Because the iron-capture stage is critical to growth, it has become a
recent focus of attention as a possible drug target. Raymond, who has
studied bacterial siderophores that capture iron for 35 years, recently
teamed up with Roland Strong of the Seattle cancer center to study
siderocalin, a human protein Strong had found that appeared to
interfere with the siderophores secreted by anthrax bacteria.
To study the role of this protein, Raymond and UC Berkeley graduate
students Rebecca J. Abergel and Trisha M. Hoette approached an anthrax
research laboratory run by B. Rowe Byers, professor of microbiology at
the University of Mississippi Medical Center, to obtain samples of
anthrax siderophores. Because bacteria secrete siderophores, these
molecules can be separated from the bacteria and studied without danger
of infection.
Using these anthrax bacteria extracts, Abergel and Hoette isolated the
two siderophores, bacillibactin and petrobactin, and showed that
siderocalin tightly binds bacillibactin, preventing it from capturing
iron from human cells. However, siderocalin does not prevent
petrobactin from binding iron.
Interestingly, bacillibactin is very similar to siderophores in other
bacteria, including enterobactin, which is produced by several
pathogenic bacteria that live in the gut, such as Salmonella enterica
and pathogenic strains of E. coli. These two bacteria also contain a
second siderophore, aerobactin, with a molecular structure similar to
petrobactin.
The researchers suggest that producing a second, stealth siderophore -
petrobactin or aerobactin - that has a different molecular structure
than bacillibactin and enterobactin may be a common response by
bacteria to the human body's production of siderocalin.
The research could lead to anti-anthrax drugs that target petrobactin
synthesis or iron-uptake, or to anthrax sensors that detect
petrobactin, which is not known to occur in any other pathogenic
bacteria.
The research was funded by the National Institutes of Health
* w w w .sciencedaily . com /releases/2006/11/061130191058.htm
Who loves ya.
Tom
Jesus Was A Vegetarian!
* jesuswasavegetarian.7h . com
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
Re: Anthrax / iron
"while studying how these deadly bacteria steal iron from their human
hosts to grow and reproduce."
Ah, Anthrax is good for us then because it reduces iron and because
"iron causes all disease because people eat meat".
"while studying how these deadly bacteria steal iron from their human
hosts to grow and reproduce."
Ah, Anthrax is good for us then because it reduces iron and because
"iron causes all disease because people eat meat".
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