# The Role of YebC in persistent infection of the Lyme disease pathogen

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $198,125

## Abstract

PROJECT ABSTRACT
Lyme disease has emerged as a major public health threat in the United States. One of the unique
features of the Lyme disease pathogen Borrelia (or Borreliella) burgdorferi (B. burgdorferi)
infection is its ability to evade immune responses and cause persistent infection in mammalian
hosts. Differential expression of surface antigens and VlsE antigen variation are two major
strategies evolved by B. burgdorferi to achieve persistence in mammals. During the transition from
early to persistent phase of infection when humoral immunity is activated, this spirochetal
pathogen downregulates OspC, a major surface antigen that is required for early phase of
infection. Concomitantly, B. burgdorferi upregulates VlsE, a surface lipoprotein that undergoes
antigen variation in mammalian hosts. How vlsE is differentially regulated and what controls vlsE
recombination are not unknown. We recently discovered a hypothetical ORF (BB0025) in the B.
burgdorferi genome, encoding a novel regulator YebC that controls vlsE expression. In this
application, we will test the hypothesis that YebC orchestrates differential expression of vlsE
during the early and persistent phases of infection (Aim 1). We will also examine whether
downregulation of ospC requires YebC during mammalian infection. In addition to regulating vlsE
expression, we provide preliminary data supporting the hypothesis that YebC is also involved in
regulating the process of vlsE recombination. This will be tested in Aim 2. Upon the successful
completion of this project, we will have identified a key regulator involving in vlsE regulation and
antigen variation. Not only will it fill a major gap in our understanding of how B. burgdorferi
upregulates vlsE expression and activate the vlsE recombination in the mammalian host, but also
will open up a new avenue for further elucidating how YebC responds to humoral immune
response or other host signals to regulates virulence gene expression. Thus, the outcome of this
application will significantly advance our understanding immune evasion and persistent infection
of B. burgdorferi and other pathogens in general.

## Key facts

- **NIH application ID:** 10527922
- **Project number:** 1R21AI169333-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** X. Frank Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,125
- **Award type:** 1
- **Project period:** 2022-05-16 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527922

## Citation

> US National Institutes of Health, RePORTER application 10527922, The Role of YebC in persistent infection of the Lyme disease pathogen (1R21AI169333-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10527922. Licensed CC0.

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