A manganese-rich environment supports superoxide dismutase activity in a lyme disease pathogen, Borrelia burgdorferi
Aguirre, J. Dafhne
Clark, Hillary M.
McIlvin, Matthew R.
Palmere, Shaina L.
Grab, Dennis J.
Hart, P. John
Saito, Mak A.
Culotta, Valeria C.
MetadataShow full item record
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.
Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 288 (2013): 8468-8478, doi:10.1074/jbc.M112.433540.
Showing items related by title, author, creator and subject.
Learman, Deric R.; Voelker, Bettina M.; Madden, Andrew S.; Hansel, Colleen M. (Frontiers Media, 2013-09-03)Manganese (Mn) oxides are among the most reactive sorbents and oxidants within the environment, where they play a central role in the cycling of nutrients, metals, and carbon. Recent discoveries have identified superoxide ...
Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis Goldstone, Jared V. (2008-10)The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of ...
The presence of four iron-containing superoxide dismutase isozymes in Trypanosomatidae : characterization, subcellular localization, and phylogenetic origin in Trypanosoma brucei Dufernez, Fabienne; Yernaux, Cedric; Gerbod, Delphine; Noel, Christophe; Chauvenet, Melanie; Wintjens, Rene; Edgcomb, Virginia P.; Capron, Monique; Opperdoes, Fred R.; Viscogliosi, Eric (2005-08-11)Metalloenzymes such as the superoxide dismutases (SODs) form part of a defense mechanism that helps protect obligate and facultative aerobic organisms from oxygen toxicity and damage. Here, we report the presence in the ...