# Testing Borrelia recurrentis isolates by using a newly developed louse-borne relapsing fever mouse model

> **NIH NIH R03** · TEXAS A&M AGRILIFE RESEARCH · 2022 · $75,750

## Abstract

PROJECT SUMMARY
Louse-borne relapsing fever (LBRF) is a human disease caused by Borrelia recurrentis. LBRF remains a
significant burden in several African nations. LBRF could account for 27% of hospital admissions. B. recurrentis
is transmitted between humans by the body louse, Pediculus humanus humanus, which is a strictly human
parasite. The mortality can be as high as 40%, if left untreated, and low as 1-5% when treated with antimicrobials.
Treatment is often problematic because up to 76% of patients exhibit a systemic antibiotic-induced reaction, the
Jarisch-Herxeimer reaction, which is associated with an elevated mortality. LBRF research has been hampered
by the lack of immunocompetent animal model. Recently, we developed an immunocompetent mouse model.
The mice consistently developed an increasing level of spirochetemia during day 1-3 pi and anti-Bre IgM
response. However, Bre was not detected from day 4 through day 10 post infection. In contrast to Bre, tick-borne
relapsing fever Borrelia (e.g., B. hermsii) have multiple peaks of spirochetemia over 7-14-day period, which is
driven by antigenic variation of Vmp proteins (products of vlsp and vsp genes) allowing spirochetes to evade
antibodies. The lack of secondary spirochetemia could be accounted for by genetic make-up of Bre antigenic
system. Recently, genomes of A17 (year of isolation, 1985) and other Bre strains, PBeK (2004), and PAbN,
PAbJ, PMaC, and PUfA (2015) were whole-genome sequenced (Marosevic et al 2017) and compared to the
reference strain A1. As a result, low genetic variability (only 29-38 SNPs) was identified between the
chromosome/plasmids for all of these strains. However, due to sequence similarity and variable numbers of
vlp/vsl genes in lp124, there was discrepant coverage of vlp/vsl genes than surrounding regions (10-20x higher),
which indicated that the numbers of vlp/vsp copies were highly variable. The latter and de novo assembly
approach taken by that study precluded identification of exact numbers and location of vlp/vsp (pseudo)genes
for the 6 sequenced Bre strains (Marosevic et al 2017). Thus, it is possible that the single relapse of
spirochetemia observed in the EE mice (and most human patients) is due to a limited repertoire of vlp/vsl system
in some Bre strains. We hypothesize that the Bre strains that possess a higher number of intact vlp/vsp
copies will develop more relapses of spirochetemia. To test it, we will pursue the following Specific Aims:
SA1: Determine the number of spirochetemic relapses that 7 Bre strains will develop in the novel LBRF
immunocompetent mouse model. SA2: Determine the exact copy numbers of intact vlp and vsp
(pseudo)genes in 7 Bre strains by using the PacBio sequencing. This is a significant and impactful proposal
because novel insights into Bre pathogenesis will be provided. This study may also improve our Bre mouse
model by having Bre strain(s) develop more than one spirochetemic cycle, which will allow us study the antigenic
...

## Key facts

- **NIH application ID:** 10447752
- **Project number:** 5R03AI163601-02
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Artem S Rogovsky
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $75,750
- **Award type:** 5
- **Project period:** 2021-07-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447752

## Citation

> US National Institutes of Health, RePORTER application 10447752, Testing Borrelia recurrentis isolates by using a newly developed louse-borne relapsing fever mouse model (5R03AI163601-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447752. Licensed CC0.

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