Differential Expression of a Putative CarD-Like Transcriptional Regulator, LtpA, in Borrelia burgdorferi

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Abstract
The availability of microbial genome information has provided a fruitful opportunity for studying regulatory networks in a variety of pathogenic bacteria. In an initial effort to elucidate regulatory networks potentially involved in differential gene expression by the Lyme disease pathogen Borrelia burgdorferi, we have been investigating the functions and regulation of putative transcriptional regulatory factors predicted to be encoded within the B. burgdorferi genome. Herein we report the regulation of one of the predicted transcriptional regulators, LtpA (BB0355), which is homologous to the transcriptional regulator CarD from Myxococcus xanthus. LtpA expression was assessed in response to various environmental stimuli. Immunoblot and quantitative reverse transcription-PCR analyses revealed that unlike many well-characterized differentially regulated Borrelia genes whose expression is induced by elevated temperature, the expression of LtpA was significantly downregulated when spirochetes were grown at an elevated temperature (37°C), as well as when the bacteria were cultivated in a mammalian host-adapted environment. In contrast, LtpA was induced at a lower culture temperature (23°C). Further analyses indicated that the downregulation of LtpA was not dependent on the Rrp2-RpoN-RpoS regulatory pathway, which is involved in the downregulation of OspA when B. burgdorferi is grown in a mammalian host-adapted environment. LtpA protein levels in B. burgdorferi were unaltered in response to changes in the pH in the borrelial cultures. Multiple attempts to generate an LtpA-deficient mutant were unsuccessful, which has hampered the elucidation of its role in pathogenesis. Given that LtpA is exclusively expressed during borrelial cultivation at a lower temperature, a parameter that has been widely used as a surrogate condition to mimic B. burgdorferi in unfed (flat) ticks, and because LtpA is homologous to a known transcriptional regulator, we postulate that LtpA functions as a regulator modulating the expression of genes important to B. burgdorferi's survival within its arthropod vector.