Bacteria require explicit control over their proteomes in order to compete and survive in dynamic environments. The Lyme disease spirochete Borrelia burgdorferi undergoes substantial protein profile changes during its cycling between vector ticks and vertebrate hosts. In an effort to understand regulation of these transitions, we recently isolated and functionally characterized the borrelial nucleic acid-binding protein BpuR, a PUR domain-containing protein. We now report that this regulatory protein governs its own synthesis through direct interactions with bpuR mRNA. In vitro and in vivo techniques indicate that BpuR binds with high affinity and specificity to the 5' region of its message, thereby inhibiting translation. This negative feedback could permit the bacteria to fine-tune cellular BpuR concentrations. These data add to the understanding of this newly described class of prokaryotic DNA- and RNA-binding regulatory proteins.