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Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A
The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conser...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244253/ https://www.ncbi.nlm.nih.gov/pubmed/28154809 http://dx.doi.org/10.3389/fcimb.2017.00009 |
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author | Wang, Jianfeng Liu, Bowen Teng, Zihao Zhou, Xuan Wang, Xiyan Zhang, Bing Lu, Gejin Niu, Xiaodi Yang, Yongjun Deng, Xuming |
author_facet | Wang, Jianfeng Liu, Bowen Teng, Zihao Zhou, Xuan Wang, Xiyan Zhang, Bing Lu, Gejin Niu, Xiaodi Yang, Yongjun Deng, Xuming |
author_sort | Wang, Jianfeng |
collection | PubMed |
description | The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conserved among the members of sortase enzyme family and cholesterol dependent toxin family. Here, phloretin, a natural polyphenolic compound derived from apples and pears that has little anti-L. monocytogenes activity, was identified to simultaneously inhibit LLO expression and neutralize SrtA catalytic activity. Phloretin neutralized SrtA activity by causing a conformational change in the protein's active pocket, which prevented engagement with its substrate. Treatment with phloretin simultaneously reduced L. monocytogenes invasion into host cells and blocked the escape of vacuole-entrapped L. monocytogenes into cytoplasm. Further, L. monocytogenes-infected mice that received phloretin showed lower mortality, decreased bacterial burden and reduced pathological injury. Our results demonstrate that phloretin is a promising anti-infective therapeutic for infections caused by L. monocytogenes due to its simultaneous targeting of SrtA and LLO, which may result in fewer side effects than those caused by other antibiotics. |
format | Online Article Text |
id | pubmed-5244253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52442532017-02-02 Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A Wang, Jianfeng Liu, Bowen Teng, Zihao Zhou, Xuan Wang, Xiyan Zhang, Bing Lu, Gejin Niu, Xiaodi Yang, Yongjun Deng, Xuming Front Cell Infect Microbiol Microbiology The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conserved among the members of sortase enzyme family and cholesterol dependent toxin family. Here, phloretin, a natural polyphenolic compound derived from apples and pears that has little anti-L. monocytogenes activity, was identified to simultaneously inhibit LLO expression and neutralize SrtA catalytic activity. Phloretin neutralized SrtA activity by causing a conformational change in the protein's active pocket, which prevented engagement with its substrate. Treatment with phloretin simultaneously reduced L. monocytogenes invasion into host cells and blocked the escape of vacuole-entrapped L. monocytogenes into cytoplasm. Further, L. monocytogenes-infected mice that received phloretin showed lower mortality, decreased bacterial burden and reduced pathological injury. Our results demonstrate that phloretin is a promising anti-infective therapeutic for infections caused by L. monocytogenes due to its simultaneous targeting of SrtA and LLO, which may result in fewer side effects than those caused by other antibiotics. Frontiers Media S.A. 2017-01-19 /pmc/articles/PMC5244253/ /pubmed/28154809 http://dx.doi.org/10.3389/fcimb.2017.00009 Text en Copyright © 2017 Wang, Liu, Teng, Zhou, Wang, Zhang, Lu, Niu, Yang and Deng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Wang, Jianfeng Liu, Bowen Teng, Zihao Zhou, Xuan Wang, Xiyan Zhang, Bing Lu, Gejin Niu, Xiaodi Yang, Yongjun Deng, Xuming Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title | Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title_full | Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title_fullStr | Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title_full_unstemmed | Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title_short | Phloretin Attenuates Listeria monocytogenes Virulence Both In vitro and In vivo by Simultaneously Targeting Listeriolysin O and Sortase A |
title_sort | phloretin attenuates listeria monocytogenes virulence both in vitro and in vivo by simultaneously targeting listeriolysin o and sortase a |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244253/ https://www.ncbi.nlm.nih.gov/pubmed/28154809 http://dx.doi.org/10.3389/fcimb.2017.00009 |
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