DksA Controls the Response of the Lyme Disease Spirochete to Starvation.

The pathogenic spirochete senses and responds to changes in the environment, including changes in nutrient availability, throughout its enzootic cycle in ticks and vertebrate hosts. This study examined the role of DnaK suppressor protein (DksA) in the transcriptional response of to starvation. Wild-type and mutant strains were subjected to starvation by shifting cultures grown in rich complete medium, Barbour-Stoenner-Kelly II (BSK II) medium, to a defined mammalian tissue culture medium, RPMI 1640, for 6 h under microaerobic conditions (5% CO, 3% O). Microarray analyses of wild-type revealed that genes encoding flagellar components, ribosomal proteins, and DNA replication machinery were downregulated in response to starvation. DksA mediated transcriptomic responses to starvation in , as the -deficient strain differentially expressed only 47 genes in response to starvation compared to the 500 genes differentially expressed in wild-type strains. Consistent with a role for DksA in the starvation response of , fewer CFU of mutants were observed after prolonged starvation in RPMI 1640 medium than CFU of wild-type spirochetes. Transcriptomic analyses revealed a partial overlap between the DksA regulon and the regulon of Rel, the guanosine tetraphosphate and guanosine pentaphosphate [(p)ppGpp] synthetase that controls the stringent response; the DksA regulon also included many plasmid-borne genes. Additionally, the mutant exhibited constitutively elevated (p)ppGpp levels compared to those of the wild-type strain, implying a regulatory relationship between DksA and (p)ppGpp. Together, these data indicate that DksA, along with (p)ppGpp, directs the stringent response to effect adaptation to its environment. The Lyme disease bacterium survives diverse environmental challenges as it cycles between its tick vectors and various vertebrate hosts. must withstand prolonged periods of starvation while it resides in unfed ticks. In this study, the regulatory protein DksA is shown to play a pivotal role controlling the transcriptional responses of to starvation. The results suggest that DksA gene regulatory activity impacts metabolism, virulence gene expression, and the ability of this bacterium to complete its natural life cycle.