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Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter

Borrelia burgdorferi is an extreme amino acid (AA) auxotroph whose genome encodes few free AA transporters and an elaborate oligopeptide transport system (B. burgdorferi Opp [BbOpp]). BbOpp consists of five oligopeptide-binding proteins (OBPs), two heterodimeric permeases, and a heterodimeric nucleo...

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Autores principales: Groshong, Ashley M., Dey, Abhishek, Bezsonova, Irina, Caimano, Melissa J., Radolf, Justin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736914/
https://www.ncbi.nlm.nih.gov/pubmed/29259089
http://dx.doi.org/10.1128/mBio.02047-17
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author Groshong, Ashley M.
Dey, Abhishek
Bezsonova, Irina
Caimano, Melissa J.
Radolf, Justin D.
author_facet Groshong, Ashley M.
Dey, Abhishek
Bezsonova, Irina
Caimano, Melissa J.
Radolf, Justin D.
author_sort Groshong, Ashley M.
collection PubMed
description Borrelia burgdorferi is an extreme amino acid (AA) auxotroph whose genome encodes few free AA transporters and an elaborate oligopeptide transport system (B. burgdorferi Opp [BbOpp]). BbOpp consists of five oligopeptide-binding proteins (OBPs), two heterodimeric permeases, and a heterodimeric nucleotide-binding domain (NBD). Homology modeling based on the crystal structure of liganded BbOppA4 revealed that each OBP likely binds a distinct range of peptides. Transcriptional analyses demonstrated that the OBPs are differentially and independently regulated whereas the permeases and NBDs are constitutively expressed. A conditional NBD mutant failed to divide in the absence of inducer and replicated in an IPTG (isopropyl-β-d-thiogalactopyranoside) concentration-dependent manner. NBD mutants grown without IPTG exhibited an elongated morphotype lacking division septa, often with flattening at the cell center due to the absence of flagellar filaments. Following cultivation in dialysis membrane chambers, NBD mutants recovered from rats not receiving IPTG also displayed an elongated morphotype. The NBD mutant was avirulent by needle inoculation, but infectivity was partially restored by oral administration of IPTG to infected mice. We conclude that peptides are a major source of AAs for B. burgdorferi both in vitro and in vivo and that peptide uptake is essential for regulation of morphogenesis, cell division, and virulence.
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spelling pubmed-57369142017-12-21 Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter Groshong, Ashley M. Dey, Abhishek Bezsonova, Irina Caimano, Melissa J. Radolf, Justin D. mBio Research Article Borrelia burgdorferi is an extreme amino acid (AA) auxotroph whose genome encodes few free AA transporters and an elaborate oligopeptide transport system (B. burgdorferi Opp [BbOpp]). BbOpp consists of five oligopeptide-binding proteins (OBPs), two heterodimeric permeases, and a heterodimeric nucleotide-binding domain (NBD). Homology modeling based on the crystal structure of liganded BbOppA4 revealed that each OBP likely binds a distinct range of peptides. Transcriptional analyses demonstrated that the OBPs are differentially and independently regulated whereas the permeases and NBDs are constitutively expressed. A conditional NBD mutant failed to divide in the absence of inducer and replicated in an IPTG (isopropyl-β-d-thiogalactopyranoside) concentration-dependent manner. NBD mutants grown without IPTG exhibited an elongated morphotype lacking division septa, often with flattening at the cell center due to the absence of flagellar filaments. Following cultivation in dialysis membrane chambers, NBD mutants recovered from rats not receiving IPTG also displayed an elongated morphotype. The NBD mutant was avirulent by needle inoculation, but infectivity was partially restored by oral administration of IPTG to infected mice. We conclude that peptides are a major source of AAs for B. burgdorferi both in vitro and in vivo and that peptide uptake is essential for regulation of morphogenesis, cell division, and virulence. American Society for Microbiology 2017-12-19 /pmc/articles/PMC5736914/ /pubmed/29259089 http://dx.doi.org/10.1128/mBio.02047-17 Text en Copyright © 2017 Groshong et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Groshong, Ashley M.
Dey, Abhishek
Bezsonova, Irina
Caimano, Melissa J.
Radolf, Justin D.
Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title_full Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title_fullStr Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title_full_unstemmed Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title_short Peptide Uptake Is Essential for Borrelia burgdorferi Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
title_sort peptide uptake is essential for borrelia burgdorferi viability and involves structural and regulatory complexity of its oligopeptide transporter
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736914/
https://www.ncbi.nlm.nih.gov/pubmed/29259089
http://dx.doi.org/10.1128/mBio.02047-17
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