Borrelia burgdorferi, the etiological agent of Lyme disease, maintains itself in nature via a complex life cycle involving an arthropod (tick) vector and small mammals. During its cycle between ticks and mammals, B. burgdorferi alters its outer surface protein profiles to interact with and adapt to these two dramatically diverse niches. For a complete understanding of Lyme disease transmission and pathogenesis, it is of major importance to discern the molecular mechanisms of borrelial host adaptation. In this regard, we recently discovered that a putative bacterial enhancer binding protein (bEBP), Rrp2, is essential for B. burgdorferi to establish infection in mammalian hosts. More importantly, our preliminary data indicate that Rrp2, distinct from other classical bEBPs, is essential for borrelial growth in vitro. These data strongly implicate Rrp2 as an atypical bEBP. This proposal seeks to elucidate the molecular bases underlying Rrp2's surprising essentiality and its unconventional activity.
In Specific Aim 1, we will assess the contributions of potential key amino acids to Rrp2's essentiality to gain initial insights into the structural basis of Rrp2's novel activity. In Specifc Aim 2, we shall identify new ?54/RpoS-independent factors influenced by Rrp2 by using global transcriptome analyses. These combined structural and functional studies will not only advance our understanding of regulatory control over borrelial virulence expression, but also account for a major paradigm-shift in our mechanistic understanding of bacterial ?54 biology.
Lyme disease, caused by the spirochetal bacterium Borrelia burgdorferi, remains the most common vector-borne illness and continues to pose public health problems in the United States. Results from this study will provide essential insights into how B. burgdorferi effectively establishes infection by precisely sensing the complex tick-mammal environments. This study also will uncover novel factors associated with borrelial infection and pathogenesis, which is directly pertinent to efforts towards the development of Lyme disease vaccines and antimicrobial strategies.
| Ouyang, Zhiming; Zhou, Jianli (2017) The putative Walker A and Walker B motifs of Rrp2 are required for the growth of Borrelia burgdorferi. Mol Microbiol 103:86-98 |
