Abstract
Lyme disease, caused by Borrelia burgdorferi, is an inflammatory multistage infection, consisting of localized, disseminated, and persistent disease stages, impacting several organ systems through poorly defined gene regulation mechanisms. The purpose of this study is to further characterize the spatiotemporal transcriptional regulation of B. burgdorferi during mammalian infection of borrelial oxidative stress regulator (bosR) and decorin binding protein (dbpBA) by utilizing bioluminescent B. burgdorferi reporter strains and in vivo imaging. Fluctuating borrelial load was also monitored and used for normalization to evaluate expression levels. bosR transcription is driven by two promoters, Pbb0648 and PbosR, and we focused on the native promoter. bosR expression is low relative to the robustly expressed dbpBA throughout infection. In distal tissues, bosR was the highest in the heart during in the first week whereas dbpBA was readily detectable at all time points with each tissue displaying a distinct expression pattern. This data suggests bosR may have a role in heart colonization and the induction of dbpBA indicates a RpoS independent transcriptional regulation occurring in the mammalian cycle of pathogenesis. These finding demonstrate that B. burgdorferi engages unknown genetic mechanisms to uniquely respond to mammalian tissue environments and/or changing host response over time.
Highlights
Lyme disease, caused by Borrelia burgdorferi, is an inflammatory multistage infection, consisting of localized, disseminated, and persistent disease stages, impacting several organ systems through poorly defined gene regulation mechanisms
In vitro characterization of B. burgdorferi bioluminescent reporter strains for borrelial oxidative stress regulator (bosR), dbpBA, and ospA
To accomplish our goal of evaluating the gene expression patterns of specific genes during murine infection, we generated B. burgdorferi bioluminescent reporter strains for bosR, dbpBA, and negative control ospA similar to our previous studies[38,39]
Summary
Lyme disease, caused by Borrelia burgdorferi, is an inflammatory multistage infection, consisting of localized, disseminated, and persistent disease stages, impacting several organ systems through poorly defined gene regulation mechanisms. This data suggests bosR may have a role in heart colonization and the induction of dbpBA indicates a RpoS independent transcriptional regulation occurring in the mammalian cycle of pathogenesis These finding demonstrate that B. burgdorferi engages unknown genetic mechanisms to uniquely respond to mammalian tissue environments and/or changing host response over time. A complex comprised of the borrelial oxidative stress regulator (BosR), response regulator 2 (Rrp2), and sigma factor (RpoN) interacts with the promoter region of transcriptional activator, rpoS Downstream in this pathway, RpoS activates expression of numerous lipoproteins including outer surface protein C (ospC) and decorin binding protein (dbpBA)[31,32]. DbpA is important for establishing a disseminated mammalian infection as it interacts with the extracellular matrices (ECM) through the binding to decorin and type I c ollagen[39,40,41,42]
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