Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin

ABSTRACT Streptococcus pneumoniae is a leading pathogen with an extracellular lifestyle; however, it is detected by cytosolic surveillance systems of macrophages. The innate immune response that follows cytosolic sensing of cell wall components results in recruitment of additional macrophages, whic...

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Autores principales:	Jamie K. Lemon, Jeffrey N. Weiser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1bcebd2047d84660a8f4e04dbbf15ec1
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spelling	oai:doaj.org-article:1bcebd2047d84660a8f4e04dbbf15ec12021-11-15T15:41:18ZDegradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin10.1128/mBio.02110-142150-7511https://doaj.org/article/1bcebd2047d84660a8f4e04dbbf15ec12015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02110-14https://doaj.org/toc/2150-7511ABSTRACT Streptococcus pneumoniae is a leading pathogen with an extracellular lifestyle; however, it is detected by cytosolic surveillance systems of macrophages. The innate immune response that follows cytosolic sensing of cell wall components results in recruitment of additional macrophages, which subsequently clear colonizing organisms from host airways. In this study, we monitored cytosolic access by following the transit of the abundant bacterial surface component capsular polysaccharide, which is linked to the cell wall. Confocal and electron microscopy visually characterized the location of cell wall components in murine macrophages outside membrane-bound organelles. Quantification of capsular polysaccharide through cellular fractionation demonstrated that cytosolic access of bacterial cell wall components is dependent on phagocytosis, bacterial sensitivity to the host’s degradative enzyme lysozyme, and release of the pore-forming toxin pneumolysin. Activation of p38 mitogen-activated protein kinase (MAPK) signaling is important for limiting access to the cytosol; however, ultimately, these are catastrophic events for both the bacteria and the macrophage, which undergoes cell death. Our results show how expression of a pore-forming toxin ensures the death of phagocytes that take up the organism, although cytosolic sensing results in innate immune detection that eventually allows for successful host defense. These findings provide an example of how cytosolic access applies to an extracellular microbe and contributes to its pathogenesis. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen that is a leading cause of pneumonia. Pneumococcal disease is preceded by colonization of the nasopharynx, which lasts several weeks before being cleared by the host’s immune system. Although S. pneumoniae is an extracellular microbe, intracellular detection of pneumococcal components is critical for bacterial clearance. In this study, we show that following bacterial uptake and degradation by phagocytes, pneumococcal products access the host cell cytosol via its pore-forming toxin. This phenomenon of cytosolic access results in phagocyte death and may serve to combat the host cells responsible for clearing the organism. Our results provide an example of how intracellular access and subsequent immune detection occurs during infection with an extracellular pathogen.Jamie K. LemonJeffrey N. WeiserAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jamie K. Lemon Jeffrey N. Weiser Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
description	ABSTRACT Streptococcus pneumoniae is a leading pathogen with an extracellular lifestyle; however, it is detected by cytosolic surveillance systems of macrophages. The innate immune response that follows cytosolic sensing of cell wall components results in recruitment of additional macrophages, which subsequently clear colonizing organisms from host airways. In this study, we monitored cytosolic access by following the transit of the abundant bacterial surface component capsular polysaccharide, which is linked to the cell wall. Confocal and electron microscopy visually characterized the location of cell wall components in murine macrophages outside membrane-bound organelles. Quantification of capsular polysaccharide through cellular fractionation demonstrated that cytosolic access of bacterial cell wall components is dependent on phagocytosis, bacterial sensitivity to the host’s degradative enzyme lysozyme, and release of the pore-forming toxin pneumolysin. Activation of p38 mitogen-activated protein kinase (MAPK) signaling is important for limiting access to the cytosol; however, ultimately, these are catastrophic events for both the bacteria and the macrophage, which undergoes cell death. Our results show how expression of a pore-forming toxin ensures the death of phagocytes that take up the organism, although cytosolic sensing results in innate immune detection that eventually allows for successful host defense. These findings provide an example of how cytosolic access applies to an extracellular microbe and contributes to its pathogenesis. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen that is a leading cause of pneumonia. Pneumococcal disease is preceded by colonization of the nasopharynx, which lasts several weeks before being cleared by the host’s immune system. Although S. pneumoniae is an extracellular microbe, intracellular detection of pneumococcal components is critical for bacterial clearance. In this study, we show that following bacterial uptake and degradation by phagocytes, pneumococcal products access the host cell cytosol via its pore-forming toxin. This phenomenon of cytosolic access results in phagocyte death and may serve to combat the host cells responsible for clearing the organism. Our results provide an example of how intracellular access and subsequent immune detection occurs during infection with an extracellular pathogen.
format	article
author	Jamie K. Lemon Jeffrey N. Weiser
author_facet	Jamie K. Lemon Jeffrey N. Weiser
author_sort	Jamie K. Lemon
title	Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
title_short	Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
title_full	Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
title_fullStr	Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
title_full_unstemmed	Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin
title_sort	degradation products of the extracellular pathogen <named-content content-type="genus-species">streptococcus pneumoniae</named-content> access the cytosol via its pore-forming toxin
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/1bcebd2047d84660a8f4e04dbbf15ec1
work_keys_str_mv	AT jamieklemon degradationproductsoftheextracellularpathogennamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentaccessthecytosolviaitsporeformingtoxin AT jeffreynweiser degradationproductsoftheextracellularpathogennamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentaccessthecytosolviaitsporeformingtoxin
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Degradation Products of the Extracellular Pathogen <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Access the Cytosol via Its Pore-Forming Toxin

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