Ironjustic
Mon, Mar-10-08, 17:16
Gallium May Have Antibiotic-Like Properties
By Michael Smith, Senior Staff Writer, MedPage Today
Published: March 16, 2007 Reviewed by Zalman S. Agus, MD;
Emeritus Professor at the University of Pennsylvania School
of Medicine.
SEATTLE, March 16 -- The metal gallium -- approved as a drug
by the FDA to treat symptomatic cancer-related hypercalcemia
-- may also be useful as an anti-microbial, according to
researchers here. Action Points
--------------------------------------------------------------
-------------------
Note that this study suggests -- on the basis of lab
experiments and studies in animals -- that the metal gallium
might be an effective antibiotic agent.
Note that the study is preliminary and more research and
ultimately human studies are needed. The metal appears to act
as a "Trojan horse" to bacteria, taking the place of iron that
the microbes need to grow and replicate, said Pradeep K.
Singh, M.D., of the University of Washington.
In mice, doses of the metal administered nasally were able to
prevent death from a lethal dose of Pseudomonas aeruginosa,
the researchers reported online in the Journal of Clinical
Investigation, in advance of the April print issue.
When the animals' lungs were pre-treated with iron, however,
the life- saving effect of the gallium was not seen, the
researchers said.
The work is based on the observation that many bacteria
require iron to grow and replicate and that many biological
defense systems operate on the principle of denying iron to
infective agents.
Gallium, a transition metal that is chemically similar to
iron, has been shown to disrupt biological mechanisms that are
dependent on iron, Dr. Singh and colleagues noted.
Their animal studies confirm a range of other in vitro
experiments, in which the metal was shown to have several
activities that might make it useful as an antibiotic, Dr.
Singh and colleagues said.
Specifically:
In culture, gallium inhibited the growth of P. aeruginosa,
including multidrug resistant strains isolated from people
with cystic fibrosis. The metal prevented P. aeruginosa from
forming biofilms involved in chronic bacterial infections. The
metal killed both free-living bacteria and bacteria in
biofilms. To test the effect of the metal in vivo, Dr. Singh
and colleagues inoculated mice with P. aeruginosa strain
PA103, at a dose that has been shown to cause death rapidly.
Three hours later, the mice were made to inhale a
50-microliter drop of either a gallium compound or a
gallium-free vehicle.
Three days after the bacterial infection, all of the
control mice had died, but more than 80% of the
gallium-treated mice were still living, a difference that
was significant at P<0.005.
When the mice were treated with an iron compound before the
gallium, they died with a similar pattern as the control
mice in the first experiment, indicating that the extra
available iron defeated the gallium "Trojan horse," the
researchers said.
The metal also inhibited the formation of biofilms in a model
in which a small plastic tube is inserted in either main
bronchus of mice, planktonic P. aeruginosa is infused, and a
biofilm forms on the tube.
Gallium or a gallium-free vehicle was administered nasally
three times a day for three days, and then the lung tissue was
tested for colony- forming units of P. aeruginosa.
The researchers found that on average, animals treated with
gallium had about 100 colony forming units per lung, compared
with about 100,000 for the untreated animals. The difference
was significant at P<0.005.
The study is limited, Dr. Singh and colleagues said, because
the animal models are not ideal, they were unable to rule out
an anti- inflammatory activity that might account for some of
the effect of gallium, and the studies did not give
information on the value of the metal in combating
established biofilms.
"Further work and, ultimately, human studies will be needed to
determine whether (gallium) is an effective antimicrobial
treatment," they concluded.
The research was supported by the Cystic Fibrosis Foundation
and the National Institutes of Health. The authors declared
they had no conflicts of interest.
Additional source: The Journal of Clinical Investigation
Source reference: Kaneko Y et al. "The transition metal
gallium disrupts Pseudomonas aeruginosa iron metabolism and
has antimicrobial and antibiofilm activity." J Clin Invest
2007; doi:10.1172/JCI30783.
Additional General Infectious Disease Coverage
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
By Michael Smith, Senior Staff Writer, MedPage Today
Published: March 16, 2007 Reviewed by Zalman S. Agus, MD;
Emeritus Professor at the University of Pennsylvania School
of Medicine.
SEATTLE, March 16 -- The metal gallium -- approved as a drug
by the FDA to treat symptomatic cancer-related hypercalcemia
-- may also be useful as an anti-microbial, according to
researchers here. Action Points
--------------------------------------------------------------
-------------------
Note that this study suggests -- on the basis of lab
experiments and studies in animals -- that the metal gallium
might be an effective antibiotic agent.
Note that the study is preliminary and more research and
ultimately human studies are needed. The metal appears to act
as a "Trojan horse" to bacteria, taking the place of iron that
the microbes need to grow and replicate, said Pradeep K.
Singh, M.D., of the University of Washington.
In mice, doses of the metal administered nasally were able to
prevent death from a lethal dose of Pseudomonas aeruginosa,
the researchers reported online in the Journal of Clinical
Investigation, in advance of the April print issue.
When the animals' lungs were pre-treated with iron, however,
the life- saving effect of the gallium was not seen, the
researchers said.
The work is based on the observation that many bacteria
require iron to grow and replicate and that many biological
defense systems operate on the principle of denying iron to
infective agents.
Gallium, a transition metal that is chemically similar to
iron, has been shown to disrupt biological mechanisms that are
dependent on iron, Dr. Singh and colleagues noted.
Their animal studies confirm a range of other in vitro
experiments, in which the metal was shown to have several
activities that might make it useful as an antibiotic, Dr.
Singh and colleagues said.
Specifically:
In culture, gallium inhibited the growth of P. aeruginosa,
including multidrug resistant strains isolated from people
with cystic fibrosis. The metal prevented P. aeruginosa from
forming biofilms involved in chronic bacterial infections. The
metal killed both free-living bacteria and bacteria in
biofilms. To test the effect of the metal in vivo, Dr. Singh
and colleagues inoculated mice with P. aeruginosa strain
PA103, at a dose that has been shown to cause death rapidly.
Three hours later, the mice were made to inhale a
50-microliter drop of either a gallium compound or a
gallium-free vehicle.
Three days after the bacterial infection, all of the
control mice had died, but more than 80% of the
gallium-treated mice were still living, a difference that
was significant at P<0.005.
When the mice were treated with an iron compound before the
gallium, they died with a similar pattern as the control
mice in the first experiment, indicating that the extra
available iron defeated the gallium "Trojan horse," the
researchers said.
The metal also inhibited the formation of biofilms in a model
in which a small plastic tube is inserted in either main
bronchus of mice, planktonic P. aeruginosa is infused, and a
biofilm forms on the tube.
Gallium or a gallium-free vehicle was administered nasally
three times a day for three days, and then the lung tissue was
tested for colony- forming units of P. aeruginosa.
The researchers found that on average, animals treated with
gallium had about 100 colony forming units per lung, compared
with about 100,000 for the untreated animals. The difference
was significant at P<0.005.
The study is limited, Dr. Singh and colleagues said, because
the animal models are not ideal, they were unable to rule out
an anti- inflammatory activity that might account for some of
the effect of gallium, and the studies did not give
information on the value of the metal in combating
established biofilms.
"Further work and, ultimately, human studies will be needed to
determine whether (gallium) is an effective antimicrobial
treatment," they concluded.
The research was supported by the Cystic Fibrosis Foundation
and the National Institutes of Health. The authors declared
they had no conflicts of interest.
Additional source: The Journal of Clinical Investigation
Source reference: Kaneko Y et al. "The transition metal
gallium disrupts Pseudomonas aeruginosa iron metabolism and
has antimicrobial and antibiofilm activity." J Clin Invest
2007; doi:10.1172/JCI30783.
Additional General Infectious Disease Coverage
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk