ARCHAEAL-TYPE LYSYL-TRANSFER-RNA SYNTHETASE IN THE LYME-DISEASE SPIROCHETE BORRELIA-BURGDORFERI

Lysyl-tRNAs are essential for protein biosynthesis by ribosomal mRNA t ranslation in all organisms. They are synthesized by lysyl-tRNA synthe tases (EC 6.1.1.6), a group of enzymes composed of two unrelated famil ies. In bacteria and eukarya, all known lysyl-tRNA synthetases are sub class IIc-type aminoacyl-tRNA synthetases, whereas some archaea have b een shown to contain an unrelated class I-type lysyl-tRNA synthetase. Examination of the preliminary genomic sequence of the bacterial patho gen Borrelia burgdorferi, the causative agent of Lyme disease, indicat ed the presence of an open reading frame with over 55% similarity at t he amino acid level to archaeal class I-type lysyl-tRNA synthetases. I n contrast, no coding region with significant similarity to any class II-type lysyl-tRNA synthetase could be detected. Heterologous expressi on of this open reading frame in Escherichia coil led to the productio n of a protein with canonical lysyl-tRNA synthetase activity in vitro. Analysis of B. burgdorferi mRNA showed that the lysyl-tRNA synthetase -encoding gene is highly expressed, confirming that B. burgdorferi con tains a functional class I-type lysyl-tRNA synthetase. The detection o f an archaeal-type lysyl-tRNA synthetase in B. burgdorferi and other p athogenic spirochetes, but not to date elsewhere in bacteria or eukary a, indicates that the gene that encodes this enzyme has a common origi n with its orthologue from the archaeal kingdom. This difference betwe en the lysyl-tRNA synthetases of spirochetes and their hosts may be re adily exploitable for the development of anti-spirochete therapeutics.