Borrelia peptidoglycan interacting Protein (BpiP) contributes to the fitness of Borrelia burgdorferi against host-derived factors and influences virulence in mouse models of Lyme disease
Abstract
The Peptidoglycan (PG) cell wall of the Lyme disease (LD) spirochete,Borrelia burgdorferi (Bb), contributes to structural and morphological integrity ofBb; is a persistent antigen in LD patients; and has a unique pentapeptide with L-Ornithine as the third amino acid that cross-links its glycan polymers. A borrelial homolog (BB_0167) interacted specifically with borrelilal PG via its peptidoglycan interacting motif (MHELSEKRARAIGNYL); was localized to the protoplasmic cylinder ofBb; and was designated asBorreliapeptidoglycaninteractingProtein (BpiP). AbpiPmutant displayed no defect underin vitrogrowth conditions with similar levels of several virulence-related proteins. However, the burden ofbpiPmutant in C3H/HeN mice at day 14, 28 and 62 post-infection was significantly lower compared to control strains. No viablebpiPmutant was re-isolated from any tissues at day 62 post-infection althoughbpiPmutant was able to colonize immunodeficient SCID at day 28 post-infection. Acquisition or transmission ofbpiPmutant byIxodes scapularislarvae or nymphs respectively, from and to mice, was significantly lower compared to control strains. Further analysis ofbpiPmutant revealed increased sensitivity to vancomycin, osmotic stress, lysosomal extracts, human antimicrobial peptide cathelicidin-LL37, complement-dependent killing in the presence of day 14 post-infection mouse serum and increased internalization of CFSC-labeledbpiPmutant by macrophages and dendritic cells compared to control strains. These studies demonstrate the importance of accessory protein/s involved in sustaining integrity of PG and cell envelope during different phases ofBbinfection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 21, 2021
- Source ID
- 10.1371/journal.ppat.1009535
Entities
People
- Floyd L. Wormley
- Janakiram Seshu
- Karen L. Wozniak
- S L Rajasekhar Karna
- Sean M. Vargas
- Taylor Macmackin Ingle
- Trever C Smith
- Yue Chen
Organizations
- Army Research Office
- Brown Foundation
- Cancer Genomics Centre
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- National Science Foundation
- University of Texas at San Antonio
- graduate school