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The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection

Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually tran...

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Autores principales: Antunes, Ana, Derkaoui, Meriem, Terrade, Aude, Denizon, Mélanie, Deghmane, Ala-Eddine, Deutscher, Josef, Delany, Isabel, Taha, Muhamed-Kheir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031443/
https://www.ncbi.nlm.nih.gov/pubmed/27655040
http://dx.doi.org/10.1371/journal.pone.0162434
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author Antunes, Ana
Derkaoui, Meriem
Terrade, Aude
Denizon, Mélanie
Deghmane, Ala-Eddine
Deutscher, Josef
Delany, Isabel
Taha, Muhamed-Kheir
author_facet Antunes, Ana
Derkaoui, Meriem
Terrade, Aude
Denizon, Mélanie
Deghmane, Ala-Eddine
Deutscher, Josef
Delany, Isabel
Taha, Muhamed-Kheir
author_sort Antunes, Ana
collection PubMed
description Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), in which the phosphocarrier protein HPr (encoded by the ptsH gene) plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and ΔptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the ΔptsH strain. The ΔptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the ΔptsH mutant. We therefore compared the transcriptomic profiles of wild-type and ΔptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43%) and several membrane-associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the ΔptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the ΔptsH strain from blood.
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spelling pubmed-50314432016-10-10 The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection Antunes, Ana Derkaoui, Meriem Terrade, Aude Denizon, Mélanie Deghmane, Ala-Eddine Deutscher, Josef Delany, Isabel Taha, Muhamed-Kheir PLoS One Research Article Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), in which the phosphocarrier protein HPr (encoded by the ptsH gene) plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and ΔptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the ΔptsH strain. The ΔptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the ΔptsH mutant. We therefore compared the transcriptomic profiles of wild-type and ΔptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43%) and several membrane-associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the ΔptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the ΔptsH strain from blood. Public Library of Science 2016-09-21 /pmc/articles/PMC5031443/ /pubmed/27655040 http://dx.doi.org/10.1371/journal.pone.0162434 Text en © 2016 Antunes 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
Antunes, Ana
Derkaoui, Meriem
Terrade, Aude
Denizon, Mélanie
Deghmane, Ala-Eddine
Deutscher, Josef
Delany, Isabel
Taha, Muhamed-Kheir
The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title_full The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title_fullStr The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title_full_unstemmed The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title_short The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection
title_sort phosphocarrier protein hpr contributes to meningococcal survival during infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031443/
https://www.ncbi.nlm.nih.gov/pubmed/27655040
http://dx.doi.org/10.1371/journal.pone.0162434
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