Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System
<i>Pseudomonas aeruginosa</i>, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/23/12699 |
| _version_ | 1797507784631123968 |
|---|---|
| author | Shiwei Wang Yuqi Feng Xiaofeng Han Xinyu Cai Liu Yang Chaolan Liu Lixin Shen |
| author_facet | Shiwei Wang Yuqi Feng Xiaofeng Han Xinyu Cai Liu Yang Chaolan Liu Lixin Shen |
| author_sort | Shiwei Wang |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i>, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective pressure on growth such as conventional antibiotics can reduce multidrug resistance in bacteria. Therefore, many quorum-sensing inhibitors (QSIs) have been developed to prevent or treat this bacterial infection. In this study, wogonin, as an active ingredient from <i>Agrimonia pilosa</i>, was found to be able to inhibit QS system of <i>P. aeruginosa</i> PAO1. Wogonin downregulated the expression of QS-related genes and reduced the production of many virulence factors, such as elastase, pyocyanin, and proteolytic enzyme. In addition, wogonin decreased the extracellular polysaccharide synthesis and inhibited twitching, swimming, and swarming motilities and biofilm formation. The attenuation of pathogenicity in <i>P. aeruginosa</i> PAO1 by wogonin application was further validated in vivo by cabbage infection and fruit fly and nematode survival experiments. Further molecular docking analysis, pathogenicity examination of various QS-related mutants, and PQS signal molecule detection revealed that wogonin could interfere with PQS signal molecular synthesis by affecting <i>pqsA</i> and <i>pqsR</i>. Taken together, the results indicated that wogonin might be used as an anti-QS candidate drug to attenuate the infection caused by <i>P. aeruginosa</i>. |
| first_indexed | 2024-03-10T04:53:21Z |
| format | Article |
| id | doaj.art-7e1bcd591d674d119d64fd6ca199e57c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:21Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7e1bcd591d674d119d64fd6ca199e57c2023-11-23T02:26:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231269910.3390/ijms222312699Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing SystemShiwei Wang0Yuqi Feng1Xiaofeng Han2Xinyu Cai3Liu Yang4Chaolan Liu5Lixin Shen6Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, ChinaAntibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, No. 168, Huaguan Road, Chengdu 610052, ChinaKey Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi’an 710069, China<i>Pseudomonas aeruginosa</i>, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective pressure on growth such as conventional antibiotics can reduce multidrug resistance in bacteria. Therefore, many quorum-sensing inhibitors (QSIs) have been developed to prevent or treat this bacterial infection. In this study, wogonin, as an active ingredient from <i>Agrimonia pilosa</i>, was found to be able to inhibit QS system of <i>P. aeruginosa</i> PAO1. Wogonin downregulated the expression of QS-related genes and reduced the production of many virulence factors, such as elastase, pyocyanin, and proteolytic enzyme. In addition, wogonin decreased the extracellular polysaccharide synthesis and inhibited twitching, swimming, and swarming motilities and biofilm formation. The attenuation of pathogenicity in <i>P. aeruginosa</i> PAO1 by wogonin application was further validated in vivo by cabbage infection and fruit fly and nematode survival experiments. Further molecular docking analysis, pathogenicity examination of various QS-related mutants, and PQS signal molecule detection revealed that wogonin could interfere with PQS signal molecular synthesis by affecting <i>pqsA</i> and <i>pqsR</i>. Taken together, the results indicated that wogonin might be used as an anti-QS candidate drug to attenuate the infection caused by <i>P. aeruginosa</i>.https://www.mdpi.com/1422-0067/22/23/12699wogonin<i>P. aeruginosa</i>quorum sensingvirulence factorsbiofilmmolecular docking |
| spellingShingle | Shiwei Wang Yuqi Feng Xiaofeng Han Xinyu Cai Liu Yang Chaolan Liu Lixin Shen Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System International Journal of Molecular Sciences wogonin <i>P. aeruginosa</i> quorum sensing virulence factors biofilm molecular docking |
| title | Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System |
| title_full | Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System |
| title_fullStr | Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System |
| title_full_unstemmed | Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System |
| title_short | Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of <i>Pseudomonas aeruginosa</i> PAO1 via Targeting <i>pqs</i> Quorum-Sensing System |
| title_sort | inhibition of virulence factors and biofilm formation by wogonin attenuates pathogenicity of i pseudomonas aeruginosa i pao1 via targeting i pqs i quorum sensing system |
| topic | wogonin <i>P. aeruginosa</i> quorum sensing virulence factors biofilm molecular docking |
| url | https://www.mdpi.com/1422-0067/22/23/12699 |
| work_keys_str_mv | AT shiweiwang inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT yuqifeng inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT xiaofenghan inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT xinyucai inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT liuyang inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT chaolanliu inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem AT lixinshen inhibitionofvirulencefactorsandbiofilmformationbywogoninattenuatespathogenicityofipseudomonasaeruginosaipao1viatargetingipqsiquorumsensingsystem |