# Regulation of infection-associated protein expressed by the Lyme disease spirochete DnaA protein

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $222,582

## Abstract

ABSTRACT 
Vector-­borne  pathogens  such  as  Borrelia  burgdorferi,  the  agent  of  Lyme  disease,  produce  different  proteins 
during  infection  of  the  mammalian  host  and  the  arthropod  vector.  These  include  distinct  surface  proteins  to 
interact  with  the  variety  of  tissues  that  are  encountered.  In  addition,  vector-­borne  bacteria  must  sense  when 
the vector is feeding on a host, and efficiently coordinate transmission processes. 
We  discovered  that  several  key  infection-­associated  proteins  that  are  produced  during  tick  feeding  and 
transmission  can  be  induced  in  culture  by  increasing  the  rate  of  bacterial  replication.  A  model  proposes  that 
this  corresponds to the dramatic  increase  in  growth  rate  of  B.  burgdorferi  when a tick  begins  to feed  on blood. 
We  found  that  the  master  regulator  of  chromosomal  replication,  the  DnaA  protein,  binds  adjacent  to  the 
transcriptional  promoters  of  loci  that  encode  two  global  regulatory  proteins.  Both  of  those  regulatory  proteins 
direct the production of surface proteins that contribute to mammalian infection processes. DnaA homologs are 
known  to  regulate  transcription  in  E.  coli  and  other  bacterial  species.  We  hypothesize  that  DnaA  serves  to 
connect borrelial replication with production of infection-­associated proteins. 
The  planned  studies  will  critically  test  that  hypothesis  by  identifying  DnaA-­binding  sites  throughout  the  B. 
burgdorferi  genome  by  chromatin  immunoprecipitation  -­  sequencing  (ChIP-­Seq),  characterizing  new  DnaA-­
regulated loci, and biochemically defining factors involved with DnaA-­binding. 
Altogether,  results  of these  studies  will  characterize a  novel  regulon  of  the Lyme  disease spirochete, providing 
substantial new insight on the bacteria’s physiology and infectious mechanisms.

## Key facts

- **NIH application ID:** 9984651
- **Project number:** 1R21AI147139-01A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Brian Stevenson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,582
- **Award type:** 1
- **Project period:** 2020-02-14 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984651

## Citation

> US National Institutes of Health, RePORTER application 9984651, Regulation of infection-associated protein expressed by the Lyme disease spirochete DnaA protein (1R21AI147139-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984651. Licensed CC0.

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