Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection
The quorum sensing (QS) circuitry of Pseudomonas aeruginosa represents an attractive target to attenuate bacterial virulence and antibiotic resistance. In this context, phytochemicals harboring anti-virulent properties have emerged as an alternative medicine to combat pseudomonal infections. Hence,...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.899566/full |
| _version_ | 1811226307995893760 |
|---|---|
| author | Jatin Chadha Ravi Jogender Singh Sanjay Chhibber Kusum Harjai |
| author_facet | Jatin Chadha Ravi Jogender Singh Sanjay Chhibber Kusum Harjai |
| author_sort | Jatin Chadha |
| collection | DOAJ |
| description | The quorum sensing (QS) circuitry of Pseudomonas aeruginosa represents an attractive target to attenuate bacterial virulence and antibiotic resistance. In this context, phytochemicals harboring anti-virulent properties have emerged as an alternative medicine to combat pseudomonal infections. Hence, this study was undertaken to investigate the synergistic effects and quorum quenching (QQ) potential of cinnamaldehyde (CiNN) in combination with gentamicin (GeN) against P. aeruginosa. The QQ activity of this novel combination was evaluated using a QS reporter strain and synergism was studied using chequerboard assays. Further, the genotypic and phenotypic expression of pseudomonal virulence factors was examined alongside biofilm formation. The combination of CiNN and GeN exhibited synergy and promising anti-QS activity. This drug combination was shown to suppress AHL production and downregulate the expression of critical QS genes in P. aeruginosa PAO1. Molecular docking revealed strong interactions between the QS receptors and CiNN, asserting its QQ potential. Bacterial motility was compromised along with a significant reduction in pyocyanin (72.3%), alginate (58.7%), rhamnolipid (33.6%), hemolysin (82.6%), protease (70.9%), and elastase (63.9%) production. The drug combination successfully eradicated preformed biofilms and inhibited biofilm formation by abrogating EPS production. Our findings suggest that although GeN alone could not attenuate QS, but was able to augment the anti-QS potential of CiNN. To validate our results using an infection model, we quantified the survival rates of Caenorhabditis elegans following PAO1 challenge. The combination significantly rescued C. elegans from PAO1 infection and improved its survival rate by 54% at 96 h. In summary, this study is the first to elucidate the mechanism behind the QQ prospects of CiNN (augmented in presence of GeN) by abrogating AHL production and increasing the survival rate of C. elegans, thereby highlighting its anti-virulent properties. |
| first_indexed | 2024-04-12T09:23:01Z |
| format | Article |
| id | doaj.art-b907bf17e7a6477fac83d5be18c0ee24 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T09:23:01Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-b907bf17e7a6477fac83d5be18c0ee242022-12-22T03:38:34ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-06-011210.3389/fcimb.2022.899566899566Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa InfectionJatin Chadha0 Ravi1Jogender Singh2Sanjay Chhibber3Kusum Harjai4Department of Microbiology, Panjab University, Chandigarh, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research (IISER), Mohali, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research (IISER), Mohali, IndiaDepartment of Microbiology, Panjab University, Chandigarh, IndiaDepartment of Microbiology, Panjab University, Chandigarh, IndiaThe quorum sensing (QS) circuitry of Pseudomonas aeruginosa represents an attractive target to attenuate bacterial virulence and antibiotic resistance. In this context, phytochemicals harboring anti-virulent properties have emerged as an alternative medicine to combat pseudomonal infections. Hence, this study was undertaken to investigate the synergistic effects and quorum quenching (QQ) potential of cinnamaldehyde (CiNN) in combination with gentamicin (GeN) against P. aeruginosa. The QQ activity of this novel combination was evaluated using a QS reporter strain and synergism was studied using chequerboard assays. Further, the genotypic and phenotypic expression of pseudomonal virulence factors was examined alongside biofilm formation. The combination of CiNN and GeN exhibited synergy and promising anti-QS activity. This drug combination was shown to suppress AHL production and downregulate the expression of critical QS genes in P. aeruginosa PAO1. Molecular docking revealed strong interactions between the QS receptors and CiNN, asserting its QQ potential. Bacterial motility was compromised along with a significant reduction in pyocyanin (72.3%), alginate (58.7%), rhamnolipid (33.6%), hemolysin (82.6%), protease (70.9%), and elastase (63.9%) production. The drug combination successfully eradicated preformed biofilms and inhibited biofilm formation by abrogating EPS production. Our findings suggest that although GeN alone could not attenuate QS, but was able to augment the anti-QS potential of CiNN. To validate our results using an infection model, we quantified the survival rates of Caenorhabditis elegans following PAO1 challenge. The combination significantly rescued C. elegans from PAO1 infection and improved its survival rate by 54% at 96 h. In summary, this study is the first to elucidate the mechanism behind the QQ prospects of CiNN (augmented in presence of GeN) by abrogating AHL production and increasing the survival rate of C. elegans, thereby highlighting its anti-virulent properties.https://www.frontiersin.org/articles/10.3389/fcimb.2022.899566/fullPseudomonas aeruginosaquorum sensingvirulencebiofilm formationcinnamaldehydeCaenorhabditis elegans |
| spellingShingle | Jatin Chadha Ravi Jogender Singh Sanjay Chhibber Kusum Harjai Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection Frontiers in Cellular and Infection Microbiology Pseudomonas aeruginosa quorum sensing virulence biofilm formation cinnamaldehyde Caenorhabditis elegans |
| title | Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection |
| title_full | Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection |
| title_fullStr | Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection |
| title_full_unstemmed | Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection |
| title_short | Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection |
| title_sort | gentamicin augments the quorum quenching potential of cinnamaldehyde in vitro and protects caenorhabditis elegans from pseudomonas aeruginosa infection |
| topic | Pseudomonas aeruginosa quorum sensing virulence biofilm formation cinnamaldehyde Caenorhabditis elegans |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.899566/full |
| work_keys_str_mv | AT jatinchadha gentamicinaugmentsthequorumquenchingpotentialofcinnamaldehydeinvitroandprotectscaenorhabditiselegansfrompseudomonasaeruginosainfection AT ravi gentamicinaugmentsthequorumquenchingpotentialofcinnamaldehydeinvitroandprotectscaenorhabditiselegansfrompseudomonasaeruginosainfection AT jogendersingh gentamicinaugmentsthequorumquenchingpotentialofcinnamaldehydeinvitroandprotectscaenorhabditiselegansfrompseudomonasaeruginosainfection AT sanjaychhibber gentamicinaugmentsthequorumquenchingpotentialofcinnamaldehydeinvitroandprotectscaenorhabditiselegansfrompseudomonasaeruginosainfection AT kusumharjai gentamicinaugmentsthequorumquenchingpotentialofcinnamaldehydeinvitroandprotectscaenorhabditiselegansfrompseudomonasaeruginosainfection |