Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.

Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bart A Eijkelkamp, Jacqueline R Morey, Miranda P Ween, Cheryl-lynn Y Ong, Alastair G McEwan, James C Paton, Christopher A McDevitt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8df264e3720c49de8a31fbe146abd13e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8df264e3720c49de8a31fbe146abd13e
record_format	dspace
spelling	oai:doaj.org-article:8df264e3720c49de8a31fbe146abd13e2021-11-18T08:32:09ZExtracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.1932-620310.1371/journal.pone.0089427https://doaj.org/article/8df264e3720c49de8a31fbe146abd13e2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24558498/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA), a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a 'toxic' effect on bacterial pathogens, such as S. pneumoniae.Bart A EijkelkampJacqueline R MoreyMiranda P WeenCheryl-lynn Y OngAlastair G McEwanJames C PatonChristopher A McDevittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89427 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bart A Eijkelkamp Jacqueline R Morey Miranda P Ween Cheryl-lynn Y Ong Alastair G McEwan James C Paton Christopher A McDevitt Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
description	Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA), a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a 'toxic' effect on bacterial pathogens, such as S. pneumoniae.
format	article
author	Bart A Eijkelkamp Jacqueline R Morey Miranda P Ween Cheryl-lynn Y Ong Alastair G McEwan James C Paton Christopher A McDevitt
author_facet	Bart A Eijkelkamp Jacqueline R Morey Miranda P Ween Cheryl-lynn Y Ong Alastair G McEwan James C Paton Christopher A McDevitt
author_sort	Bart A Eijkelkamp
title	Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
title_short	Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
title_full	Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
title_fullStr	Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
title_full_unstemmed	Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
title_sort	extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in streptococcus pneumoniae.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8df264e3720c49de8a31fbe146abd13e
work_keys_str_mv	AT bartaeijkelkamp extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT jacquelinermorey extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT mirandapween extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT cheryllynnyong extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT alastairgmcewan extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT jamescpaton extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae AT christopheramcdevitt extracellularzinccompetitivelyinhibitsmanganeseuptakeandcompromisesoxidativestressmanagementinstreptococcuspneumoniae
_version_	1718421696287866880

Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.

Ejemplares similares