Grants and Contracts Details
All organisms, from bacteria to humans, need to “recognize” where they are, and respond accordingly. A pathogen must sense its location in the infectious cycle, then produce factors necessary for that site while repressing synthesis of inappropriate factors. Thus, disruption of key regulatory pathways can inhibit a pathogen’s ability to infect, indicating useful targets for developing novel antibiotics. In our studies of the Lyme disease bacterium, Borrelia burgdorferi, we discovered that a new DNA/RNA-binding protein named Bpur is essential for optimal mammalian infection. B. burgdorferi regulates production of Bpur, synthesizing it at low levels during mammalian infection processes, and at much higher levels during colonization of vector ticks. We genetically engineered B. burgdorferi to constitutively produce high levels of Bpur during murine infection, and found the mutant to be significantly impaired in its ability to colonize mice. Transcriptomic analyses (RNA-Seq) demonstrated that Bpur significantly effects expression of approximately 5% of B. burgdorferi genes, dysregulating cellular levels of numerous known virulence factors and metabolic enzymes. To enhance understanding of the roles of Bpur in B. burgdorferi physiology and pathogenesis, we will define the mechanisms by which B. burgdorferi controls cellular levels of Bpur.
|Effective start/end date||2/10/16 → 1/31/19|
- National Institute of Allergy and Infectious Diseases: $408,157.00
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