Lyme spirochetes are unusual in that they do
not require iron. The authors of this newly published paper found that
Borrelia burgdorferi also has "the capacity to accumulate remarkably
high levels of manganese. This high manganese is necessary to activate
the SodA superoxide dismutase (SOD) essential for virulence."
http://www.jbc.org/content/early/2013/02/02/jbc.M112.433540
Background: SodA is an important virulence factor in Borrelia burgdorferi.
Results: This SodA
requires extraordinarily high intracellular manganese for activity, and
accumulates as either manganese or apo-protein,
but not iron-bound.
Conclusion: B. burgdorferi SodA is a unique Mn-SOD based on metal requirements and predicted structure.
Significance: B. burgdorferi pathogenicity may be controlled by exploiting the unusual properties of SodA.
A Manganese-Rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi
The Lyme disease pathogen Borrelia burgdorferi represents a novel
organism in which to study metalloprotein biology in that
this spirochete has uniquely evolved with no
requirement for iron. Not only is iron low, but we show here that B.
burgdorferi
has the capacity to accumulate remarkably high
levels of manganese. This high manganese is necessary to activate the
SodA
superoxide dismutase (SOD) essential for virulence.
Using a metalloproteomic approach, we demonstrate that a bulk of B.
burgdorferi
SodA directly associates with manganese and a
smaller pool of inactive enzyme accumulates as apoprotein. Other
metalloproteins
may have similarly adapted to using manganese as
co-factor including the BB0366 amino-peptidase. While B. burgdorferi
SodA
has evolved in a manganese-rich, iron-poor
environment, the opposite is true for Mn-SODs of organisms such as E.
coli and
bakers yeast. These Mn-SODs still capture manganese
in an iron-rich cell, and we tested whether the same is true for
Borrelia
SodA. When expressed in the iron-rich mitochondria
of S. cerevisiae, B. burgdorferi SodA was inactive. Activity was only
possible
when cells accumulated extremely high levels of
manganese that exceeded cellular iron. Moreover, there was no evidence
for
iron inactivation of the SOD. B. burgdorferi SodA
shows strong overall homology with other members of the Mn-SOD family,
but
computer assisted modeling revealed some unusual
features of the hydrogen bonding network near the enzyme's active site.
The
unique properties of B. burgdorferi SodA may
represent adaptation to expression in the manganese-rich and iron-poor
environment
of the spirochete.
