Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.

Borrelia burgdorferi must acquire all of its amino acids (AAs) from its arthropod vector and vertebrate host. Previously, we determined that peptide uptake via the oligopeptide (Opp) ABC transporter is essential for spirochete viability in vitro and during infection. Our prior study also suggested t...

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Autores principales:	Ashley M Groshong, Melissa A McLain, Justin D Radolf
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/612b4e6168da43228e1f33b7c1ec450c
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spelling	oai:doaj.org-article:612b4e6168da43228e1f33b7c1ec450c2021-12-02T20:00:18ZHost-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.1553-73661553-737410.1371/journal.ppat.1009180https://doaj.org/article/612b4e6168da43228e1f33b7c1ec450c2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009180https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Borrelia burgdorferi must acquire all of its amino acids (AAs) from its arthropod vector and vertebrate host. Previously, we determined that peptide uptake via the oligopeptide (Opp) ABC transporter is essential for spirochete viability in vitro and during infection. Our prior study also suggested that B. burgdorferi employs temporal regulation in concert with structural variation of oligopeptide-binding proteins (OppAs) to meet its AA requirements in each biological niche. Herein, we evaluated the contributions to the B. burgdorferi enzootic cycle of three of the spirochete's five OppAs (OppA1, OppA2, and OppA5). An oppA1 transposon (tn) mutant lysed in the hyperosmolar environment of the feeding tick, suggesting that OppA1 imports amino acids required for osmoprotection. The oppA2tn mutant displayed a profound defect in hematogenous dissemination in mice, yet persisted within skin while inducing only a minimal antibody response. These results, along with slightly decreased growth of the oppA2tn mutant within DMCs, suggest that OppA2 serves a minor nutritive role, while its dissemination defect points to an as yet uncharacterized signaling function. Previously, we identified a role for OppA5 in spirochete persistence within the mammalian host. We now show that the oppA5tn mutant displayed no defect during the tick phase of the cycle and could be tick-transmitted to naïve mice. Instead of working in tandem, however, OppA2 and OppA5 appear to function in a hierarchical manner; the ability of OppA5 to promote persistence relies upon the ability of OppA2 to facilitate dissemination. Structural homology models demonstrated variations within the binding pockets of OppA1, 2, and 5 indicative of different peptide repertoires. Rather than being redundant, B. burgdorferi's multiplicity of Opp binding proteins enables host-specific functional compartmentalization during the spirochete lifecycle.Ashley M GroshongMelissa A McLainJustin D RadolfPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 1, p e1009180 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ashley M Groshong Melissa A McLain Justin D Radolf Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
description	Borrelia burgdorferi must acquire all of its amino acids (AAs) from its arthropod vector and vertebrate host. Previously, we determined that peptide uptake via the oligopeptide (Opp) ABC transporter is essential for spirochete viability in vitro and during infection. Our prior study also suggested that B. burgdorferi employs temporal regulation in concert with structural variation of oligopeptide-binding proteins (OppAs) to meet its AA requirements in each biological niche. Herein, we evaluated the contributions to the B. burgdorferi enzootic cycle of three of the spirochete's five OppAs (OppA1, OppA2, and OppA5). An oppA1 transposon (tn) mutant lysed in the hyperosmolar environment of the feeding tick, suggesting that OppA1 imports amino acids required for osmoprotection. The oppA2tn mutant displayed a profound defect in hematogenous dissemination in mice, yet persisted within skin while inducing only a minimal antibody response. These results, along with slightly decreased growth of the oppA2tn mutant within DMCs, suggest that OppA2 serves a minor nutritive role, while its dissemination defect points to an as yet uncharacterized signaling function. Previously, we identified a role for OppA5 in spirochete persistence within the mammalian host. We now show that the oppA5tn mutant displayed no defect during the tick phase of the cycle and could be tick-transmitted to naïve mice. Instead of working in tandem, however, OppA2 and OppA5 appear to function in a hierarchical manner; the ability of OppA5 to promote persistence relies upon the ability of OppA2 to facilitate dissemination. Structural homology models demonstrated variations within the binding pockets of OppA1, 2, and 5 indicative of different peptide repertoires. Rather than being redundant, B. burgdorferi's multiplicity of Opp binding proteins enables host-specific functional compartmentalization during the spirochete lifecycle.
format	article
author	Ashley M Groshong Melissa A McLain Justin D Radolf
author_facet	Ashley M Groshong Melissa A McLain Justin D Radolf
author_sort	Ashley M Groshong
title	Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
title_short	Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
title_full	Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
title_fullStr	Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
title_full_unstemmed	Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.
title_sort	host-specific functional compartmentalization within the oligopeptide transporter during the borrelia burgdorferi enzootic cycle.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/612b4e6168da43228e1f33b7c1ec450c
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Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle.

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