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Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation...

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Autores principales: Talyansky, Yuli, Nielsen, Travis B., Yan, Jun, Carlino-Macdonald, Ulrike, Di Venanzio, Gisela, Chakravorty, Somnath, Ulhaq, Amber, Feldman, Mario F., Russo, Thomas A., Vinogradov, Evgeny, Luna, Brian, Wright, Meredith S., Adams, Mark D., Spellberg, Brad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880449/
https://www.ncbi.nlm.nih.gov/pubmed/33529209
http://dx.doi.org/10.1371/journal.ppat.1009291
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author Talyansky, Yuli
Nielsen, Travis B.
Yan, Jun
Carlino-Macdonald, Ulrike
Di Venanzio, Gisela
Chakravorty, Somnath
Ulhaq, Amber
Feldman, Mario F.
Russo, Thomas A.
Vinogradov, Evgeny
Luna, Brian
Wright, Meredith S.
Adams, Mark D.
Spellberg, Brad
author_facet Talyansky, Yuli
Nielsen, Travis B.
Yan, Jun
Carlino-Macdonald, Ulrike
Di Venanzio, Gisela
Chakravorty, Somnath
Ulhaq, Amber
Feldman, Mario F.
Russo, Thomas A.
Vinogradov, Evgeny
Luna, Brian
Wright, Meredith S.
Adams, Mark D.
Spellberg, Brad
author_sort Talyansky, Yuli
collection PubMed
description Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis.
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spelling pubmed-78804492021-02-19 Capsule carbohydrate structure determines virulence in Acinetobacter baumannii Talyansky, Yuli Nielsen, Travis B. Yan, Jun Carlino-Macdonald, Ulrike Di Venanzio, Gisela Chakravorty, Somnath Ulhaq, Amber Feldman, Mario F. Russo, Thomas A. Vinogradov, Evgeny Luna, Brian Wright, Meredith S. Adams, Mark D. Spellberg, Brad PLoS Pathog Research Article Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis. Public Library of Science 2021-02-02 /pmc/articles/PMC7880449/ /pubmed/33529209 http://dx.doi.org/10.1371/journal.ppat.1009291 Text en © 2021 Talyansky et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Talyansky, Yuli
Nielsen, Travis B.
Yan, Jun
Carlino-Macdonald, Ulrike
Di Venanzio, Gisela
Chakravorty, Somnath
Ulhaq, Amber
Feldman, Mario F.
Russo, Thomas A.
Vinogradov, Evgeny
Luna, Brian
Wright, Meredith S.
Adams, Mark D.
Spellberg, Brad
Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title_full Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title_fullStr Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title_full_unstemmed Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title_short Capsule carbohydrate structure determines virulence in Acinetobacter baumannii
title_sort capsule carbohydrate structure determines virulence in acinetobacter baumannii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880449/
https://www.ncbi.nlm.nih.gov/pubmed/33529209
http://dx.doi.org/10.1371/journal.ppat.1009291
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