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The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst

Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the inte...

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Autores principales: Coady, Alison, Xu, Min, Phung, Qui, Cheung, Tommy K., Bakalarski, Corey, Alexander, Mary Kate, Lehar, Sophie M., Kim, Janice, Park, Summer, Tan, Man-Wah, Nishiyama, Mireille
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574778/
https://www.ncbi.nlm.nih.gov/pubmed/26379037
http://dx.doi.org/10.1371/journal.pone.0138350
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author Coady, Alison
Xu, Min
Phung, Qui
Cheung, Tommy K.
Bakalarski, Corey
Alexander, Mary Kate
Lehar, Sophie M.
Kim, Janice
Park, Summer
Tan, Man-Wah
Nishiyama, Mireille
author_facet Coady, Alison
Xu, Min
Phung, Qui
Cheung, Tommy K.
Bakalarski, Corey
Alexander, Mary Kate
Lehar, Sophie M.
Kim, Janice
Park, Summer
Tan, Man-Wah
Nishiyama, Mireille
author_sort Coady, Alison
collection PubMed
description Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host.
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spelling pubmed-45747782015-09-25 The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst Coady, Alison Xu, Min Phung, Qui Cheung, Tommy K. Bakalarski, Corey Alexander, Mary Kate Lehar, Sophie M. Kim, Janice Park, Summer Tan, Man-Wah Nishiyama, Mireille PLoS One Research Article Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host. Public Library of Science 2015-09-17 /pmc/articles/PMC4574778/ /pubmed/26379037 http://dx.doi.org/10.1371/journal.pone.0138350 Text en © 2015 Coady 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Coady, Alison
Xu, Min
Phung, Qui
Cheung, Tommy K.
Bakalarski, Corey
Alexander, Mary Kate
Lehar, Sophie M.
Kim, Janice
Park, Summer
Tan, Man-Wah
Nishiyama, Mireille
The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title_full The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title_fullStr The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title_full_unstemmed The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title_short The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst
title_sort staphylococcus aureus abc-type manganese transporter mntabc is critical for reinitiation of bacterial replication following exposure to phagocytic oxidative burst
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574778/
https://www.ncbi.nlm.nih.gov/pubmed/26379037
http://dx.doi.org/10.1371/journal.pone.0138350
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