Evidence That Two ATP-Dependent (Lon) Proteases in Borrelia burgdorferi Serve Different Functions

PLoS Pathogens

Jorge L. Benach¹  Alvaro Toledo²  Nihal A. Okan²  Laura I. Katona²  Christopher Kuhlow²  Rafal Tokarz²  James L. Coleman³ 

[1] Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, New York, United States of America;Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, United States of America;State of New York Department of Health, Stony Brook University, Stony Brook, New York, United States of America

关键词: Borrelia burgdorferi;    Proteases;    Insulin;    Spirochetes;    Borrelia;    Phylogenetic analysis;    Blood;    Lyme disease;   

DOI  :  10.1371/journal.ppat.1000676

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 NH2-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.

【 授权许可】

CC BY