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Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC
QseC is a membrane-bound histidine sensor kinase found in Gram-negative pathogens and is involved in the regulation of bacterial virulence. LED209, a QseC-specific inhibitor, significantly inhibits the virulence of several pathogens and partially protects infected mice from death by blocking QseC. H...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112599/ https://www.ncbi.nlm.nih.gov/pubmed/27853287 http://dx.doi.org/10.1038/srep37447 |
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author | Li, Zhi Zheng, Qing Xue, Xiaoyan Shi, Xin Zhou, Ying Da, Fei Qu, Di Hou, Zheng Luo, Xiaoxing |
author_facet | Li, Zhi Zheng, Qing Xue, Xiaoyan Shi, Xin Zhou, Ying Da, Fei Qu, Di Hou, Zheng Luo, Xiaoxing |
author_sort | Li, Zhi |
collection | PubMed |
description | QseC is a membrane-bound histidine sensor kinase found in Gram-negative pathogens and is involved in the regulation of bacterial virulence. LED209, a QseC-specific inhibitor, significantly inhibits the virulence of several pathogens and partially protects infected mice from death by blocking QseC. However, the mechanism of its antibacterial effects remains unclear. In this experiment, a Salmonella Typhimurium (S. Typhimurium) and macrophage co-culture system was utilized to investigate possible mechanisms underlying the antimicrobial effects of the QseC inhibitor. QseC blockade inhibited the expression of QseC-dependent virulence genes, including flhDC, sifA, and sopB, in S. Typhimurium, leading to inhibition of swimming motility, invasion capacity, and replication capacity of the pathogens. Release of lactate dehydrogenase (LDH) from S. Typhimurium-infected macrophages was significantly inhibited by blocking QseC. Activated caspase-1 and IL-1β levels were suppressed, and intracellular bacterial count was reduced in infected macrophages. QseC blockade effectively reduced the virulence of S. Typhimurium, inhibited S. Typhimurium-induced pyroptosis of macrophages, and promoted elimination of intracellular bacteria from infected macrophages. Thus, the antibacterial effects of QseC inhibitor are mediated via enhancement of intracellular killing of S. Typhimurium in macrophages. |
format | Online Article Text |
id | pubmed-5112599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51125992016-11-25 Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC Li, Zhi Zheng, Qing Xue, Xiaoyan Shi, Xin Zhou, Ying Da, Fei Qu, Di Hou, Zheng Luo, Xiaoxing Sci Rep Article QseC is a membrane-bound histidine sensor kinase found in Gram-negative pathogens and is involved in the regulation of bacterial virulence. LED209, a QseC-specific inhibitor, significantly inhibits the virulence of several pathogens and partially protects infected mice from death by blocking QseC. However, the mechanism of its antibacterial effects remains unclear. In this experiment, a Salmonella Typhimurium (S. Typhimurium) and macrophage co-culture system was utilized to investigate possible mechanisms underlying the antimicrobial effects of the QseC inhibitor. QseC blockade inhibited the expression of QseC-dependent virulence genes, including flhDC, sifA, and sopB, in S. Typhimurium, leading to inhibition of swimming motility, invasion capacity, and replication capacity of the pathogens. Release of lactate dehydrogenase (LDH) from S. Typhimurium-infected macrophages was significantly inhibited by blocking QseC. Activated caspase-1 and IL-1β levels were suppressed, and intracellular bacterial count was reduced in infected macrophages. QseC blockade effectively reduced the virulence of S. Typhimurium, inhibited S. Typhimurium-induced pyroptosis of macrophages, and promoted elimination of intracellular bacteria from infected macrophages. Thus, the antibacterial effects of QseC inhibitor are mediated via enhancement of intracellular killing of S. Typhimurium in macrophages. Nature Publishing Group 2016-11-17 /pmc/articles/PMC5112599/ /pubmed/27853287 http://dx.doi.org/10.1038/srep37447 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Li, Zhi Zheng, Qing Xue, Xiaoyan Shi, Xin Zhou, Ying Da, Fei Qu, Di Hou, Zheng Luo, Xiaoxing Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title | Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title_full | Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title_fullStr | Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title_full_unstemmed | Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title_short | Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC |
title_sort | pyroptosis of salmonella typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking qsec |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112599/ https://www.ncbi.nlm.nih.gov/pubmed/27853287 http://dx.doi.org/10.1038/srep37447 |
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