# A novel antimicrobial resistance mechanism for Borrelia burgdorferi

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $227,250

## Abstract

PROJECT SUMMARY
The etiologic agent of Lyme disease, Borreliella burgdorferi, is a spirochetal bacterium that represents the
most common arthropod-based infection in the United States. Each year Lyme disease contributes to
significant morbidity in patients within endemic areas as well as for those who suffer from post treatment
Lyme disease syndrome. B. burgdorferi is considered an extracellular pathogen and, as such, must
contend with the host response to colonize and persist in the face of active innate and adaptive immunity.
Prior studies demonstrated that conditions mimicking mammalian infection induce the expression of
BosR/RpoN/RpoS-regulated virulence associated B. burgdorferi genes, including ospC, dbpBA, and
bbk32. In addition to these genes, other loci that are coordinately regulated have been identified but the
proteins they encode have no known function(s). Many groups, including the Skare and Höök labs, have
focused on surface exposed proteins to determine how they interface with host structures to promote the
pathogenic potential of B. burgdorferi. One limitation in determining function is the lack of homology that
these borrelial proteins share with virulence associated proteins from other pathogens. The dearth of
information of how these surface exposed proteins contribute to the establishment and maintenance of B.
burgdorferi infectivity and pathogenesis represents a significant gap in the current knowledge base. One
such borrelial gene/protein that fits this description is bbk53/BBK53 and its paralogues. Preliminary data
presented herein indicates that recombinant BBK53 binds to human dermcidin (hDCD), an anionic
antimicrobial peptide that is produced by dermal fibroblasts. Subsequently, the Skare and Höök groups
found that B. burgdorferi lacking bbk53 were more sensitive to hDCD relative to its isogenic parent and
complement strains. These results suggest that B. burgdorferi BBK53 binds to hDCD and prevents the
integration of this lethal peptide into borrelial membranes, most notably the energized cytoplasmic
membrane, and thus reduces innate killing of these spirochetes during initial infection within the skin. This
hypothesis will be tested with the following Specific Aims: (1) Characterize the interactions between
BBK53::hDCD and hDCD derivatives; and (2) Determine if BBK53 provides an hDCD-dependent survival
advantage to B. burgdorferi following in vitro infection. The role described here for BBK53 is significant as
it represents the first anionic antimicrobial peptide resistance mechanism observed for B. burgdorferi. As
such, BBK53 may reduce innate clearance of B. burgdorferi, promote colonization of the skin, and provide
a larger pool of spirochetes for subsequent dissemination into deeper tissues.

## Key facts

- **NIH application ID:** 10425475
- **Project number:** 1R21AI168397-01
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** JON T SKARE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $227,250
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425475

## Citation

> US National Institutes of Health, RePORTER application 10425475, A novel antimicrobial resistance mechanism for Borrelia burgdorferi (1R21AI168397-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10425475. Licensed CC0.

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