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A borrelial homolog (BB_0167) interacted specifically with borrelilal PG via its peptidoglycan interacting motif (MHELSEKRARAIGNYL); was localized to the protoplasmic cylinder of<jats:italic>Bb<\/jats:italic>; and was designated as<jats:underline>B<\/jats:underline>orrelia<jats:underline>p<\/jats:underline>eptidoglycan<jats:underline>i<\/jats:underline>nteracting<jats:underline>P<\/jats:underline>rotein (BpiP). A<jats:italic>bpiP<\/jats:italic>mutant displayed no defect under<jats:italic>in vitro<\/jats:italic>growth conditions with similar levels of several virulence-related proteins. However, the burden of<jats:italic>bpiP<\/jats:italic>mutant in C3H\/HeN mice at day 14, 28 and 62 post-infection was significantly lower compared to control strains. No viable<jats:italic>bpiP<\/jats:italic>mutant was re-isolated from any tissues at day 62 post-infection although<jats:italic>bpiP<\/jats:italic>mutant was able to colonize immunodeficient SCID at day 28 post-infection. Acquisition or transmission of<jats:italic>bpiP<\/jats:italic>mutant by<jats:italic>Ixodes scapularis<\/jats:italic>larvae or nymphs respectively, from and to mice, was significantly lower compared to control strains. Further analysis of<jats:italic>bpiP<\/jats:italic>mutant 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-labeled<jats:italic>bpiP<\/jats:italic>mutant 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 of<jats:italic>Bb<\/jats:italic>infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009535","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T22:48:23Z","timestamp":1619045303000},"page":"e1009535","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["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"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-5236","authenticated-orcid":true,"given":"Yue","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-980X","authenticated-orcid":true,"given":"Sean M.","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1651-313X","authenticated-orcid":true,"given":"Trever C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1876-7117","authenticated-orcid":true,"given":"Sai Lakshmi Rajasekhar","family":"Karna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"MacMackin Ingle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-2146","authenticated-orcid":true,"given":"Karen L.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floyd L.","family":"Wormley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-2435","authenticated-orcid":true,"given":"Janakiram","family":"Seshu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"issue":"5","key":"ppat.1009535.ref001","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/cid\/ciu397","article-title":"Lyme disease testing by large commercial laboratories in the United States","volume":"59","author":"AF 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