A Manganese-Rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi
Jessica Dafhne Aguirre1,
Hillary M. Clark1,
Matthew McIlvin2,
Christine Vazquez1,
Shaina L. Palmere1,
Dennis Grab1,
JanaKiram Seshu3,
P. John Hart3,
Mak Saito2 and
Valeria C. Culotta1,*
- Author Affiliations
1 Johns Hopkins University, United States;
2 Woods Hole Oceanographic Institution, United States;
3 University of Texas, San Antonio, United States
↵* Corresponding author; email: []
Capsule
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.
Abstract
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.
Received November 2, 2012.
Accepted February 2, 2013.
Copyright ? 2013, The American Society for Biochemistry and Molecular Biology
