Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi

Abstract Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to bacterial evasion of the host innate immune system. To investigate the molecular mechanism of serum-resistance, we construct...

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Main Authors: Kozue Sato, Yumi Kumagai, Tsuyoshi Sekizuka, Makoto Kuroda, Tetsuya Hayashi, Ai Takano, Gaowa, Kyle R. Taylor, Makoto Ohnishi, Hiroki Kawabata
Format: Article
Language:English
Published: Nature Portfolio 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-85069-w
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author Kozue Sato
Yumi Kumagai
Tsuyoshi Sekizuka
Makoto Kuroda
Tetsuya Hayashi
Ai Takano
Gaowa
Kyle R. Taylor
Makoto Ohnishi
Hiroki Kawabata
author_facet Kozue Sato
Yumi Kumagai
Tsuyoshi Sekizuka
Makoto Kuroda
Tetsuya Hayashi
Ai Takano
Gaowa
Kyle R. Taylor
Makoto Ohnishi
Hiroki Kawabata
author_sort Kozue Sato
collection DOAJ
description Abstract Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to bacterial evasion of the host innate immune system. To investigate the molecular mechanism of serum-resistance, we constructed a membrane protein-encoding gene library of B. miyamotoi using Borrelia garinii strain HT59G, which shows a transformable and serum-susceptible phenotype. By screening the library, we found that bom1093 and bom1515 of B. miyamotoi provided a serum-resistant phenotype to the recipient B. garinii. These B. miyamotoi genes are predicted to encode P35-like antigen genes and are conserved among relapsing fever borreliae. Functional analysis revealed that BOM1093 bound to serum vitronectin and that the C-terminal region of BOM1093 was involved in the vitronectin-binding property. Importantly, the B. garinii transformant was not serum-resistant when the C terminus-truncated BOM1093 was expressed. We also observed that the depletion of vitronectin from human serum enhances the bactericidal activity of BOM1093 expressing B. garinii, and the survival rate of BOM1093 expressing B. garinii in vitronectin-depleted serum is enhanced by the addition of purified vitronectin. Our data suggests that B. miyamotoi utilize BOM1093-mediated binding to vitronectin as a mechanism of serum resistance.
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spelling doaj.art-1ca93b4dd78d42f4a47f6c2bc832432d2022-12-21T22:58:11ZengNature PortfolioScientific Reports2045-23222021-03-0111111310.1038/s41598-021-85069-wVitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoiKozue Sato0Yumi Kumagai1Tsuyoshi Sekizuka2Makoto Kuroda3Tetsuya Hayashi4Ai Takano5Gaowa6Kyle R. Taylor7Makoto Ohnishi8Hiroki Kawabata9Department of Bacteriology-I, National Institute of Infectious DiseaseDepartment of Bacteriology-I, National Institute of Infectious DiseasePathogen Genomics Center, National Institute of Infectious DiseasePathogen Genomics Center, National Institute of Infectious DiseaseDepartment of Bacteriology, Faculty of Medical Sciences, Kyushu UniversityLaboratory of Veterinary Epidemiology, Joint Faculty of Veterinary Medicine, Yamaguchi UniversityInner Mongolia Key Laboratory of Tick-Borne Zoonotic Infectious Disease, Department of Medicine, College of HetaoCollege of Veterinary Medicine, Washington State UniversityDepartment of Bacteriology-I, National Institute of Infectious DiseaseDepartment of Bacteriology-I, National Institute of Infectious DiseaseAbstract Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to bacterial evasion of the host innate immune system. To investigate the molecular mechanism of serum-resistance, we constructed a membrane protein-encoding gene library of B. miyamotoi using Borrelia garinii strain HT59G, which shows a transformable and serum-susceptible phenotype. By screening the library, we found that bom1093 and bom1515 of B. miyamotoi provided a serum-resistant phenotype to the recipient B. garinii. These B. miyamotoi genes are predicted to encode P35-like antigen genes and are conserved among relapsing fever borreliae. Functional analysis revealed that BOM1093 bound to serum vitronectin and that the C-terminal region of BOM1093 was involved in the vitronectin-binding property. Importantly, the B. garinii transformant was not serum-resistant when the C terminus-truncated BOM1093 was expressed. We also observed that the depletion of vitronectin from human serum enhances the bactericidal activity of BOM1093 expressing B. garinii, and the survival rate of BOM1093 expressing B. garinii in vitronectin-depleted serum is enhanced by the addition of purified vitronectin. Our data suggests that B. miyamotoi utilize BOM1093-mediated binding to vitronectin as a mechanism of serum resistance.https://doi.org/10.1038/s41598-021-85069-w
spellingShingle Kozue Sato
Yumi Kumagai
Tsuyoshi Sekizuka
Makoto Kuroda
Tetsuya Hayashi
Ai Takano
Gaowa
Kyle R. Taylor
Makoto Ohnishi
Hiroki Kawabata
Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
Scientific Reports
title Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
title_full Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
title_fullStr Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
title_full_unstemmed Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
title_short Vitronectin binding protein, BOM1093, confers serum resistance on Borrelia miyamotoi
title_sort vitronectin binding protein bom1093 confers serum resistance on borrelia miyamotoi
url https://doi.org/10.1038/s41598-021-85069-w
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