Francisella tularensis requires iron (Fe) for growth, but the biologic
sources
of Fe for this organism are largely unknown.
We found that Francisella sp. growing in broth culture or within
human
macrophages can acquire Fe from the two major host Fe binding
proteins,
lactoferrin (Lf) and transferrin (Tf).
Fe acquisition is a potential target for novel therapies.
Gallium (Ga) is a transition metal that interferes with cellular Fe
metabolism
by competing with Fe for uptake/utilization.
Growth of either F. tularensis LVS (LVS) or F. novicida was inhibited
by
>/=2 muM Ga chelated to Tf or Lf, with GaLf somewhat more potent.
Francisella sp. express two Fe-containing antioxidant enzymes,
catalase
(KatG) and Fe co-factored superoxide dismutase (Fe-SOD).
Growth of LVS with 10 muM GaTf or GaLf led to a dramatic decrease in
bacterial catalase activity and in Fe-SOD activity that was associated
with
an increased susceptibility to H2O2.
Ga also protected mice from intranasal challenge with F. novicida.
Where 100% of the F. novicida infected mice died by day 9, 75% of the
mice
receiving Ga continued to survive to at least day 15.
Thus, a single intransal dose of Ga followed by daily intraperitoneal
Ga at a
dose tolerated by the animals resulted in prolonged survival.
These data support the potential utility of Ga as a therapy for F.
tularensis
infection of the lung.
PMID: 19917753
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
The human body has systems in place to regulate iron uptake, which in
large part controls the level of iron in the body. Now for the millions
of those suffering from the world's number one health problem, low iron,
this substance would not be advisable.
It is because you are .. stupid ..
DO YOU UNDERSTAND .. ?
GALLIUM DISRUPTS IRON UPTAKE BY INTRACELLULAR AND
EXTRACELLULAR FRANCISELLA AND EXHIBITS THERAPEUTIC
EFFICACY IN A MURINE PULMONARY INFECTION MODEL.