Spermine and Spermidine Alter Gene Expression and Antigenic Profile of Borrelia burgdorferi

Abstract

<i>Borrelia burgdorferi</i>, the agent of Lyme disease, responds to numerous host-derived signals to alter adaptive capabilities during its enzootic cycle in an arthropod vector and mammalian host. Molecular mechanisms that enable <i>B. burgdorferi</i> to detect, channel, and respond to these signals have become an intense area of study for developing strategies to limit transmission/infection. Bioinformatic analysis of the borrelial genome revealed the presence of polyamine transport components (PotA, PotB, PotC, and PotD), while homologs for polyamine biosynthesis were conspicuously absent. Although <i>potABCD</i> is cotranscribed, the level of PotA was elevated under <i>in vitro</i> growth conditions mimicking unfed ticks compared to the level in fed ticks, while the levels of PotD were similar under the aforementioned conditions in <i>B. burgdorferi</i> Among several polyamines and polyamine precursors, supplementation of spermine or spermidine in the borrelial growth medium induced synthesis of major regulators of gene expression in <i>B. burgdorferi</i>, such as RpoS and BosR, with a concomitant increase in proteins that contribute to colonization and survival of <i>B. burgdorferi</i> in the mammalian host. Short transcripts of <i>rpoS</i> were elevated in response to spermidine, which was correlated with increased protein levels of RpoS. Transcriptional analysis of <i>rpoZ</i> and <i>B. burgdorferi</i><i>rel</i> (<i>rel_Bbu</i> ; <i>bb0198</i>) in the presence of spermidine revealed the interplay of multiple regulatory factors in <i>B. burgdorferi</i> gene expression. The effect of spermidine on the levels of select borrelial proteins was also influenced by serum factors. These studies suggest that multiple host-derived signals/nutrients and their transport systems contribute to <i>B. burgdorferi</i> adaptation during the vector and vertebrate host phases of infection.