Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling.

Content Provider	Europe PMC
Author	Li, Xia Wang, Kai Wang, Gerun Cui, Binbin Song, Shihao Sun, Xiuyun Deng, Yinyue
Editor	Rampioni, Giordano
Copyright Year	2022
Abstract	ABSTRACTBurkholderia 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.
Page Count	15
Volume Number	10
PubMed Central reference number	PMC9430380
Issue Number	4
PubMed reference number	35856676
Journal	Microbiology Spectrum [Microbiol Spectr]
e-ISSN	21650497
DOI	10.1128/spectrum.01787-22
Language	English
Publisher	American Society for Microbiology
Publisher Date	2022-07-20
Publisher Place	N.W., Washington, DC
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Copyright © 2022 Li et al.
Subject Keyword	Burkholderia cenocepacia quorum sensing BDSF AHL oridonin
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology Infectious Diseases Immunology and Microbiology Genetics Microbiology (medical) Ecology