Project 1: Function of surface exposed proteins in borrelial infection and pathogenesis
Borreliella burgdorferi—the agent of Lyme disease—is known to change its gene expression and protein production in response to its host environments. These fascinating bacterial pathogens can colonize and survive within both arthropods (ticks) and mammals despite having simplistic genomic content. Within these two distinct living systems, B. burgdorferi uses surface-exposed proteins to colonize hosts they infect, evade the host immune response, and persist.
The lab has identified and/or characterized several surface proteins that bind to connective tissue and host proteins that impair immune function. Regarding the latter activity, together with Brandon Garcia’s group at East Carolina University, we have found that the BBK32 protein from B. burgdorferi can inhibit the classical complement pathway. This is an additional activity that is likely to prevent clearance and promote persistent infection.
We have identified homologues of BBK32-like proteins in relapsing fever Borrelia species, a related but distinct set of pathogenic spirochetes. Interestingly, and unlike the Lyme disease spirochete, relapsing fever Borrelia make multiple copies of proteins that inhibit the classical complement cascade. We are currently looking into the role(s) of these various proteins.
Project 2: Understanding how Borrelia adapts to the different environments it can occupy.
The Skare Lab is also interested in global regulatory pathways that affect borrelial transmission, colonization, and persistence, including transcriptional and post-transcriptional regulation. In addition to the deletion and characterization of virulence determinants in borrelial infectivity, this work involves transcriptional regulators (e.g., BosR) as well as the characterization of small non-coding RNAs (sRNAs). sRNAs bind to transcripts, with or without proteins, and direct their turnover or enhances translation.
In collaboration with Jenny Hyde (Texas A&M) and Meghan Lybecker (CDC)—the Skare lab provided the first molecular genetic analysis and analysis of an sRNA in borrelial infectivity and pathogenesis. This collaboration has resulted in the recent identification of a new borrelial chaperone that recognizes RNA, including sRNAs.
sRNAs bound by this chaperone that play a role in borrelial virulence are being evaluated to determine the transcripts that they recognize and modulate to assess this form of post-transcriptional regulation and how it applies to borrelial pathogenesis.
