A novel iron- and copper-binding protein in the Lyme disease spirochaete.
Iron and copper are transition metals that can be toxic to cells due to their abilities to react with peroxide to generate hydroxyl radical. Ferritins and metallothioneins are known to sequester intracellular iron and copper respectively. The Lyme disease pathogen Borrelia burgdorferi does not require iron, but its genome encodes a ferritin-like Dps (DNA-binding protein from starved bacteria) molecule, which has been shown to be important for the spirochaete's persistence in the tick and subsequent transmission to a new host. Here, we show that the carboxyl-terminal cysteine-rich (CCR) domain of this protein functions as a copper-binding metallothionein. This novel fusion between Dps and metallothionein is unique to and conserved in all Borrelia species. We term this molecule BicA for Borrelia iron- and copper-binding protein A. An isogenic mutant lacking BicA had significantly reduced levels of iron and copper and was more sensitive to iron and copper toxicity than its parental strain. Supplementation of the medium with iron or copper rendered the spirochaete more susceptible to peroxide killing. These data suggest that an important function of BicA is to detoxify excess iron and copper the spirochaete may encounter during its natural life cycle through a tick vector and a vertebrate host.
Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
Peng
P
Wang
Anthony
A
Lutton
John
J
Olesik
Hojatollah
H
Vali
Xin
X
Li
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000378:metabolism* / Q000633:toxicity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D050296:Microbial Viability / Q000187:drug effects; D010545:Peroxides / Q000633:toxicity
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C083911:DPS protein, Bacteria; D010545:Peroxides; C023548:copper-binding protein; D003300:Copper; D007501:Iron