title: Evidence that two ATP-dependent (Lon) proteases in Borrelia burgdorferi serve different functions.
abstract: The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. Borrelia spirochetes are unusual in that they code for two putative ATP-dependent Lon homologs, Lon-1 and Lon-2. Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted through the blood feeding of Ixodes ticks. Previous work in our laboratory reported that B. burgdorferi lon-1 is upregulated transcriptionally by exposure to blood in vitro, while lon-2 is not. Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. Phylogenetic analysis revealed that Lon-1 and Lon-2 cluster separately due to differences in the NH(2)-terminal substrate binding domains that may reflect differences in substrate specificity. Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. We conclude that B. burgdorferi Lons -1 and -2 have distinct functional roles. Lon-2 functions in a manner consistent with canonical Lon, engaged in cellular homeostasis. Lon-1, by virtue of its blood induction, and as a unique feature of the Borreliae, may be important in host adaptation from the arthropod to a warm-blooded host.
authors: State of New York Department of Health, Stony Brook University, Stony Brook, New York, United States of America. jcoleman@notes.cc.sunysb.edu
authors: James L
authors: JL
authors: Coleman
authors: Laura I
authors: LI
authors: Katona
authors: Christopher
authors: C
authors: Kuhlow
authors: Alvaro
authors: A
authors: Toledo
authors: Nihal A
authors: NA
authors: Okan
authors: Rafal
authors: R
authors: Tokarz
authors: Jorge L
authors: JL
authors: Benach
mesh_terms: D049069:ATP-Dependent Proteases / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D001769:Blood; D025065:Borrelia burgdorferi / Q000201:enzymology*; D015964:Gene Expression Regulation, Bacterial; D008193:Lyme Disease; D049070:Protease La / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D049069:ATP-Dependent Proteases; D049070:Protease La