Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents
Background: Most nosocomial infections are caused by bacteria that proliferate within quorum sensing mediated biofilms. The disruption of quorum sensing signals in biofilm-forming bacteria is the potential substitution strategy. Purpose: The current study focuses on the evaluation of isolated juglon...
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Elsevier
2025-02-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031324001726 |
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| author | Muhammad Abdullah Bhatti Atif Ali Khan Khalil Sayed Muhammad Ata Ullah Shah Bukhari Faisal Hanif Mi-Jeong Ahn Sumra Wajid Abbasi Nazir Ahmed Lone Wen-Jun Li Wasim Sajjad |
| author_facet | Muhammad Abdullah Bhatti Atif Ali Khan Khalil Sayed Muhammad Ata Ullah Shah Bukhari Faisal Hanif Mi-Jeong Ahn Sumra Wajid Abbasi Nazir Ahmed Lone Wen-Jun Li Wasim Sajjad |
| author_sort | Muhammad Abdullah Bhatti |
| collection | DOAJ |
| description | Background: Most nosocomial infections are caused by bacteria that proliferate within quorum sensing mediated biofilms. The disruption of quorum sensing signals in biofilm-forming bacteria is the potential substitution strategy. Purpose: The current study focuses on the evaluation of isolated juglone derivatives from Reynoutria japonica as anti-biofilm agents and enzyme inhibitors against Methicillin Resistant Staphylococcus aureus (MRSA). Methods: The antibacterial and anti-biofilm activity of the juglone derivatives were investigated against laboratory strains MRSA using well and disc diffusion method. In addition, we evaluated the anti-biofilm inhibition potential of the juglone derivatives using a crystal violet-based assay in 96-well micro-titer plate. The suppression of S. aureus β-hemolytic, coagulase and proteolytic activity was evaluated using standard assay protocols. High Performance Liquid Chromatography (HPLC) was performed to analyze the acyl homoserine lactones (AHLs) signals degradation by juglone derivatives. Furthermore, all three ligand molecules were docked into the binding site of the S. aureus coagulase protein. Results: All the three juglone derivatives showed potent antimicrobial activity against clinical strains of MRSA. Among these compounds, 2-ethoxy-6-acetyl-7-methyljuglone displayed potent inhibitory activity with zones of inhibition of 15 ± 0.03 and 17 ± 0.03 against MRSA respectively. In the spectrophotometric assay, we confirmed that juglone derivatives inhibit biofilm formation. All the compounds markedly inhibited the coagulase, β-hemolytic and proteolytic activity of MRSA. The application of compounds as a treatment resulted in a notable decrease in biofilm density and thickness, as demonstrated by HPLC. The untreated MRSA exhibited quorum sensing signals of N-Butanoyl-l-homoserine lactone (C4-HSL) with retention time 3.6 min and of N-hexanoyl-l-Homoserine lactone (C6-HSL) at 5.8 minutes’ vs the treated with MRSA where no peaks were observed. The docking studies and Molecular dynamics (MD) simulation results revealed that all molecules are actively binding in the target site that correlates well with the in-vitro inhibitory properties of compounds against S. aureus. Conclusion: our results demonstrated the potential of juglone derivatives from R. japonica as a promising anti-biofilm agent and as quorum quencher for future therapy to combat multi-drug resistant infections in particular MRSA. |
| format | Article |
| id | doaj-art-3e0f943a02ca48ef99ce55af35d51374 |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Phytomedicine Plus |
| spelling | doaj-art-3e0f943a02ca48ef99ce55af35d513742025-02-10T04:35:10ZengElsevierPhytomedicine Plus2667-03132025-02-0151100698Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agentsMuhammad Abdullah Bhatti0Atif Ali Khan Khalil1Sayed Muhammad Ata Ullah Shah Bukhari2Faisal Hanif3Mi-Jeong Ahn4Sumra Wajid Abbasi5Nazir Ahmed Lone6Wen-Jun Li7Wasim Sajjad8Department of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, PakistanDepartment of Pharmacognosy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, PakistanDepartment of Microbiology, Army Medical College, National University of Medical Sciences, Rawalpindi-46000, Punjab, PakistanCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongnam 52828, South KoreaDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, PakistanSchool of Life Sciences, Sun Yat-Sen University, New Biology Buildings, Xingang West Road, Guangzhou, 510275, China; Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, ChinaDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, Pakistan; Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, China; Corresponding author at: Department of Biological Sciences, National University of Medical Sciences, Rawalpindi-46000, Punjab, Pakistan.Background: Most nosocomial infections are caused by bacteria that proliferate within quorum sensing mediated biofilms. The disruption of quorum sensing signals in biofilm-forming bacteria is the potential substitution strategy. Purpose: The current study focuses on the evaluation of isolated juglone derivatives from Reynoutria japonica as anti-biofilm agents and enzyme inhibitors against Methicillin Resistant Staphylococcus aureus (MRSA). Methods: The antibacterial and anti-biofilm activity of the juglone derivatives were investigated against laboratory strains MRSA using well and disc diffusion method. In addition, we evaluated the anti-biofilm inhibition potential of the juglone derivatives using a crystal violet-based assay in 96-well micro-titer plate. The suppression of S. aureus β-hemolytic, coagulase and proteolytic activity was evaluated using standard assay protocols. High Performance Liquid Chromatography (HPLC) was performed to analyze the acyl homoserine lactones (AHLs) signals degradation by juglone derivatives. Furthermore, all three ligand molecules were docked into the binding site of the S. aureus coagulase protein. Results: All the three juglone derivatives showed potent antimicrobial activity against clinical strains of MRSA. Among these compounds, 2-ethoxy-6-acetyl-7-methyljuglone displayed potent inhibitory activity with zones of inhibition of 15 ± 0.03 and 17 ± 0.03 against MRSA respectively. In the spectrophotometric assay, we confirmed that juglone derivatives inhibit biofilm formation. All the compounds markedly inhibited the coagulase, β-hemolytic and proteolytic activity of MRSA. The application of compounds as a treatment resulted in a notable decrease in biofilm density and thickness, as demonstrated by HPLC. The untreated MRSA exhibited quorum sensing signals of N-Butanoyl-l-homoserine lactone (C4-HSL) with retention time 3.6 min and of N-hexanoyl-l-Homoserine lactone (C6-HSL) at 5.8 minutes’ vs the treated with MRSA where no peaks were observed. The docking studies and Molecular dynamics (MD) simulation results revealed that all molecules are actively binding in the target site that correlates well with the in-vitro inhibitory properties of compounds against S. aureus. Conclusion: our results demonstrated the potential of juglone derivatives from R. japonica as a promising anti-biofilm agent and as quorum quencher for future therapy to combat multi-drug resistant infections in particular MRSA.http://www.sciencedirect.com/science/article/pii/S2667031324001726Multi-drug resistanceQuorum QuenchingJuglone derivativesNaphthoquinonesBiofilmMethicillin resistant Staphylococcus aureus |
| spellingShingle | Muhammad Abdullah Bhatti Atif Ali Khan Khalil Sayed Muhammad Ata Ullah Shah Bukhari Faisal Hanif Mi-Jeong Ahn Sumra Wajid Abbasi Nazir Ahmed Lone Wen-Jun Li Wasim Sajjad Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents Phytomedicine Plus Multi-drug resistance Quorum Quenching Juglone derivatives Naphthoquinones Biofilm Methicillin resistant Staphylococcus aureus |
| title | Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents |
| title_full | Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents |
| title_fullStr | Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents |
| title_full_unstemmed | Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents |
| title_short | Breaking the biofilm barrier: Juglone derivatives as dual-action inhibitors and anti-quorum sensing agents |
| title_sort | breaking the biofilm barrier juglone derivatives as dual action inhibitors and anti quorum sensing agents |
| topic | Multi-drug resistance Quorum Quenching Juglone derivatives Naphthoquinones Biofilm Methicillin resistant Staphylococcus aureus |
| url | http://www.sciencedirect.com/science/article/pii/S2667031324001726 |
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