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Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins
Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individual...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930693/ https://www.ncbi.nlm.nih.gov/pubmed/24586678 http://dx.doi.org/10.1371/journal.pone.0089308 |
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author | Yanai, Machi Rocha, Miguel A. Matolek, Anthony Z. Chintalacharuvu, Archana Taira, Yasuhiko Chintalacharuvu, Koteswara Beenhouwer, David O. |
author_facet | Yanai, Machi Rocha, Miguel A. Matolek, Anthony Z. Chintalacharuvu, Archana Taira, Yasuhiko Chintalacharuvu, Koteswara Beenhouwer, David O. |
author_sort | Yanai, Machi |
collection | PubMed |
description | Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individually and assemble on cell surfaces to form hetero-oligomeric pores resulting in lysis of PMNs and/or erythrocytes. F and S proteins of γ-hemolysin, PVL and LukDE have ∼70% sequence homology within the same class and several heterologous combinations of F and S members from these three bicomponent toxin groups are functional. Recently, an additional BCL pair, LukGH (also called LukAB) that has only 30% homology to γ-hemolysin, PVL and LukDE, has been characterized from S. aureus. Our results showed that LukGH was more cytotoxic to human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was markedly attenuated and slower than that induced by PVL and other staphylococcal BCLs. In contrast to other heterologous BCL combinations, LukG in combination with heterologous S components, and LukH in combination with heterologous F components did not induce calcium ion entry or cell lysis in human PMNs or rabbit erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual components LukG and LukH had no cytolytic or calcium influx activity, they each induced high levels of IL-8 transcription and secretion. IL-8 production induced by LukG or LukH was dependent on NF-κB. Therefore, our results indicate LukGH differs functionally from other staphylococcal BCLs. |
format | Online Article Text |
id | pubmed-3930693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39306932014-02-25 Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins Yanai, Machi Rocha, Miguel A. Matolek, Anthony Z. Chintalacharuvu, Archana Taira, Yasuhiko Chintalacharuvu, Koteswara Beenhouwer, David O. PLoS One Research Article Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individually and assemble on cell surfaces to form hetero-oligomeric pores resulting in lysis of PMNs and/or erythrocytes. F and S proteins of γ-hemolysin, PVL and LukDE have ∼70% sequence homology within the same class and several heterologous combinations of F and S members from these three bicomponent toxin groups are functional. Recently, an additional BCL pair, LukGH (also called LukAB) that has only 30% homology to γ-hemolysin, PVL and LukDE, has been characterized from S. aureus. Our results showed that LukGH was more cytotoxic to human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was markedly attenuated and slower than that induced by PVL and other staphylococcal BCLs. In contrast to other heterologous BCL combinations, LukG in combination with heterologous S components, and LukH in combination with heterologous F components did not induce calcium ion entry or cell lysis in human PMNs or rabbit erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual components LukG and LukH had no cytolytic or calcium influx activity, they each induced high levels of IL-8 transcription and secretion. IL-8 production induced by LukG or LukH was dependent on NF-κB. Therefore, our results indicate LukGH differs functionally from other staphylococcal BCLs. Public Library of Science 2014-02-20 /pmc/articles/PMC3930693/ /pubmed/24586678 http://dx.doi.org/10.1371/journal.pone.0089308 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Yanai, Machi Rocha, Miguel A. Matolek, Anthony Z. Chintalacharuvu, Archana Taira, Yasuhiko Chintalacharuvu, Koteswara Beenhouwer, David O. Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title | Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title_full | Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title_fullStr | Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title_full_unstemmed | Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title_short | Separately or Combined, LukG/LukH Is Functionally Unique Compared to Other Staphylococcal Bicomponent Leukotoxins |
title_sort | separately or combined, lukg/lukh is functionally unique compared to other staphylococcal bicomponent leukotoxins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930693/ https://www.ncbi.nlm.nih.gov/pubmed/24586678 http://dx.doi.org/10.1371/journal.pone.0089308 |
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