A plasmid‐encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host

Summary Borrelia burgdorferi, a spirochaete that causes Lyme borreliosis, contains 21 linear and circular plasmids thought to be important for survival in mammals or ticks. Our results demonstrate that the gene BBE22 encoding a nicotinamidase is capable of replacing the requirement for the 25 kb lin...

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Bibliographic Details
Published in:Molecular microbiology 2003-05, Vol.48 (3), p.753-764
Main Authors: Purser, Joye E., Lawrenz, Matthew B., Caimano, Melissa J., Howell, Jerrilyn K., Radolf, Justin D., Norris, Steven J.
Format: Article
Language:English
Subjects:
Animals
Bacteria
Borrelia burgdorferi - enzymology
Borrelia burgdorferi - genetics
Borrelia burgdorferi - pathogenicity
Genes
Genetic Complementation Test
Infections
Inflammation - metabolism
Joints - microbiology
Joints - pathology
Lyme Disease - metabolism
Mammals
Membranes, Artificial
Mice
Mice, Inbred C3H
Mice, SCID
Microbiology
Mutation
Nicotinamidase - genetics
Nicotinamidase - metabolism
Parasites
Plasmids - genetics
Plasmids - metabolism
Rats
Salmonella typhimurium - genetics
Salmonella typhimurium - metabolism
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Summary:Summary Borrelia burgdorferi, a spirochaete that causes Lyme borreliosis, contains 21 linear and circular plasmids thought to be important for survival in mammals or ticks. Our results demonstrate that the gene BBE22 encoding a nicotinamidase is capable of replacing the requirement for the 25 kb linear plasmid lp25 during mammalian infection. Transformation of B. burgdorferi lacking lp25 with a shuttle vector containing the lp25 gene BBE22 (pBBE22) restored infectivity in mice to a level comparable to that of wild‐type Borrelia. This complementation also restored the growth and host adaptation of lp25–B. burgdorferi in dialysis membrane chambers (DMCs) implanted in rats. A single Cys to Ala conversion at the putative active site of BBE22 abrogated the ability of pBBE22 to re‐establish infectivity or growth in DMCs. Additional Salmonella typhimurium complementation studies and enzymatic analysis demonstrated that the BBE22 gene product has nicotinamidase activity and is most probably required for the biosynthesis of NAD. These results indicate that some plasmid‐encoded products fulfil physiological functions required in the enzootic cycle of pathogenic Borrelia.
ISSN:0950-382X
1365-2958
DOI:10.1046/j.1365-2958.2003.03452.x