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A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii

Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which incl...

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Autores principales: Bateman, Thomas J., Shah, Megha, Ho, Timothy Pham, Shin, Hyejin Esther, Pan, Chuxi, Harris, Greg, Fegan, Jamie E., Islam, Epshita A., Ahn, Sang Kyun, Hooda, Yogesh, Gray-Owen, Scott D., Chen, Wangxue, Moraes, Trevor F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560813/
https://www.ncbi.nlm.nih.gov/pubmed/34725337
http://dx.doi.org/10.1038/s41467-021-26545-9
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author Bateman, Thomas J.
Shah, Megha
Ho, Timothy Pham
Shin, Hyejin Esther
Pan, Chuxi
Harris, Greg
Fegan, Jamie E.
Islam, Epshita A.
Ahn, Sang Kyun
Hooda, Yogesh
Gray-Owen, Scott D.
Chen, Wangxue
Moraes, Trevor F.
author_facet Bateman, Thomas J.
Shah, Megha
Ho, Timothy Pham
Shin, Hyejin Esther
Pan, Chuxi
Harris, Greg
Fegan, Jamie E.
Islam, Epshita A.
Ahn, Sang Kyun
Hooda, Yogesh
Gray-Owen, Scott D.
Chen, Wangxue
Moraes, Trevor F.
author_sort Bateman, Thomas J.
collection PubMed
description Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
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spelling pubmed-85608132021-11-15 A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii Bateman, Thomas J. Shah, Megha Ho, Timothy Pham Shin, Hyejin Esther Pan, Chuxi Harris, Greg Fegan, Jamie E. Islam, Epshita A. Ahn, Sang Kyun Hooda, Yogesh Gray-Owen, Scott D. Chen, Wangxue Moraes, Trevor F. Nat Commun Article Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs. Nature Publishing Group UK 2021-11-01 /pmc/articles/PMC8560813/ /pubmed/34725337 http://dx.doi.org/10.1038/s41467-021-26545-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bateman, Thomas J.
Shah, Megha
Ho, Timothy Pham
Shin, Hyejin Esther
Pan, Chuxi
Harris, Greg
Fegan, Jamie E.
Islam, Epshita A.
Ahn, Sang Kyun
Hooda, Yogesh
Gray-Owen, Scott D.
Chen, Wangxue
Moraes, Trevor F.
A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title_full A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title_fullStr A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title_full_unstemmed A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title_short A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
title_sort slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen acinetobacter baumannii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560813/
https://www.ncbi.nlm.nih.gov/pubmed/34725337
http://dx.doi.org/10.1038/s41467-021-26545-9
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