Cargando…

Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling

Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and pathogenicity: the cis-2-dodecenoic acid (BDSF) system and the N-acyl homoserine lactone (AHL) system. In this study, we reported t...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Xia, Wang, Kai, Wang, Gerun, Cui, Binbin, Song, Shihao, Sun, Xiuyun, Deng, Yinyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430380/
https://www.ncbi.nlm.nih.gov/pubmed/35856676
http://dx.doi.org/10.1128/spectrum.01787-22
_version_ 1784779753419440128
author Li, Xia
Wang, Kai
Wang, Gerun
Cui, Binbin
Song, Shihao
Sun, Xiuyun
Deng, Yinyue
author_facet Li, Xia
Wang, Kai
Wang, Gerun
Cui, Binbin
Song, Shihao
Sun, Xiuyun
Deng, Yinyue
author_sort Li, Xia
collection PubMed
description Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and pathogenicity: the cis-2-dodecenoic acid (BDSF) system and the N-acyl homoserine lactone (AHL) system. In this study, we reported that oridonin, which was screened from a collection of natural products, disrupted important B. cenocepacia phenotypes, including motility, biofilm formation, protease production, and virulence. Genetic and biochemical analyses showed that oridonin inhibited the production of BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Furthermore, we revealed that oridonin directly binds to the regulator RqpR of the two-component system RqpSR that dominates the above-mentioned QS systems to inhibit the expression of the BDSF and AHL signal synthase-encoding genes. Oridonin also binds to the transcriptional regulator CepR of the cep AHL system to inhibit its binding to the promoter of bclACB. These findings suggest that oridonin could potentially be developed as a new QS inhibitor against pathogenic B. cenocepacia. IMPORTANCE Burkholderia cenocepacia is an important human opportunistic pathogen that can cause life-threatening infections in susceptible individuals. It employs quorum-sensing (QS) systems to regulate biological functions and virulence. In this study, we have identified a lead compound, oridonin, that is capable of interfering with B. cenocepacia QS signaling and physiology. We demonstrate that oridonin suppressed cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) signal production and attenuated virulence in B. cenocepacia. Oridonin also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that oridonin could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.
format Online
Article
Text
id pubmed-9430380
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-94303802022-09-01 Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling Li, Xia Wang, Kai Wang, Gerun Cui, Binbin Song, Shihao Sun, Xiuyun Deng, Yinyue Microbiol Spectr Research Article Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and pathogenicity: the cis-2-dodecenoic acid (BDSF) system and the N-acyl homoserine lactone (AHL) system. In this study, we reported that oridonin, which was screened from a collection of natural products, disrupted important B. cenocepacia phenotypes, including motility, biofilm formation, protease production, and virulence. Genetic and biochemical analyses showed that oridonin inhibited the production of BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Furthermore, we revealed that oridonin directly binds to the regulator RqpR of the two-component system RqpSR that dominates the above-mentioned QS systems to inhibit the expression of the BDSF and AHL signal synthase-encoding genes. Oridonin also binds to the transcriptional regulator CepR of the cep AHL system to inhibit its binding to the promoter of bclACB. These findings suggest that oridonin could potentially be developed as a new QS inhibitor against pathogenic B. cenocepacia. IMPORTANCE Burkholderia cenocepacia is an important human opportunistic pathogen that can cause life-threatening infections in susceptible individuals. It employs quorum-sensing (QS) systems to regulate biological functions and virulence. In this study, we have identified a lead compound, oridonin, that is capable of interfering with B. cenocepacia QS signaling and physiology. We demonstrate that oridonin suppressed cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) signal production and attenuated virulence in B. cenocepacia. Oridonin also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that oridonin could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent. American Society for Microbiology 2022-07-20 /pmc/articles/PMC9430380/ /pubmed/35856676 http://dx.doi.org/10.1128/spectrum.01787-22 Text en Copyright © 2022 Li et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Li, Xia
Wang, Kai
Wang, Gerun
Cui, Binbin
Song, Shihao
Sun, Xiuyun
Deng, Yinyue
Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title_full Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title_fullStr Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title_full_unstemmed Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title_short Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
title_sort oridonin attenuates burkholderia cenocepacia virulence by suppressing quorum-sensing signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430380/
https://www.ncbi.nlm.nih.gov/pubmed/35856676
http://dx.doi.org/10.1128/spectrum.01787-22
work_keys_str_mv AT lixia oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT wangkai oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT wanggerun oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT cuibinbin oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT songshihao oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT sunxiuyun oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling
AT dengyinyue oridoninattenuatesburkholderiacenocepaciavirulencebysuppressingquorumsensingsignaling