Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ
Rhodomyrtone, a natural antimicrobial compound, displays potent activity against many Gram-positive pathogenic bacteria, comparable to last-defence antibiotics including vancomycin and daptomycin. Our previous studies pointed towards effects of rhodomyrtone on the bacterial membrane and cell wall. I...
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PeerJ Inc.
2017-02-01
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| author | Dennapa Saeloh Michaela Wenzel Thanyada Rungrotmongkol Leendert Willem Hamoen Varomyalin Tipmanee Supayang Piyawan Voravuthikunchai |
| author_facet | Dennapa Saeloh Michaela Wenzel Thanyada Rungrotmongkol Leendert Willem Hamoen Varomyalin Tipmanee Supayang Piyawan Voravuthikunchai |
| author_sort | Dennapa Saeloh |
| collection | DOAJ |
| description | Rhodomyrtone, a natural antimicrobial compound, displays potent activity against many Gram-positive pathogenic bacteria, comparable to last-defence antibiotics including vancomycin and daptomycin. Our previous studies pointed towards effects of rhodomyrtone on the bacterial membrane and cell wall. In addition, a recent molecular docking study suggested that the compound could competitively bind to the main bacterial cell division protein FtsZ. In this study, we applied a computational approach (in silico), in vitro, and in vivo experiments to investigate molecular interactions of rhodomyrtone with FtsZ. Using molecular simulation, FtsZ conformational changes were observed in both (S)- and (R)-rhodomyrtone binding states, compared with the three natural states of FtsZ (ligand-free, GDP-, and GTP-binding states). Calculations of free binding energy showed a higher affinity of FtsZ to (S)-rhodomyrtone (−35.92 ± 0.36 kcal mol−1) than the GDP substrate (−23.47 ± 0.25 kcal mol−1) while less affinity was observed in the case of (R)-rhodomyrtone (−18.11 ± 0.11 kcal mol−1). In vitro experiments further revealed that rhodomyrtone reduced FtsZ polymerization by 36% and inhibited GTPase activity by up to 45%. However, the compound had no effect on FtsZ localization in Bacillus subtilis at inhibitory concentrations and cells also did not elongate after treatment. Higher concentrations of rhodomyrtone did affect localization of FtsZ and also affected localization of its membrane anchor proteins FtsA and SepF, showing that the compound did not specifically inhibit FtsZ but rather impaired multiple divisome proteins. Furthermore, a number of cells adopted a bean-like shape suggesting that rhodomyrtone possibly possesses further targets involved in cell envelope synthesis and/or maintenance. |
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| language | English |
| last_indexed | 2024-03-09T06:52:16Z |
| publishDate | 2017-02-01 |
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| spelling | doaj.art-9b9263f1831d4b0cb973d621c7f846162023-12-03T10:22:40ZengPeerJ Inc.PeerJ2167-83592017-02-015e296210.7717/peerj.2962Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZDennapa Saeloh0Michaela Wenzel1Thanyada Rungrotmongkol2Leendert Willem Hamoen3Varomyalin Tipmanee4Supayang Piyawan Voravuthikunchai5Excellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, ThailandBacterial Cell Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsDepartment of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, ThailandBacterial Cell Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsExcellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, ThailandExcellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, ThailandRhodomyrtone, a natural antimicrobial compound, displays potent activity against many Gram-positive pathogenic bacteria, comparable to last-defence antibiotics including vancomycin and daptomycin. Our previous studies pointed towards effects of rhodomyrtone on the bacterial membrane and cell wall. In addition, a recent molecular docking study suggested that the compound could competitively bind to the main bacterial cell division protein FtsZ. In this study, we applied a computational approach (in silico), in vitro, and in vivo experiments to investigate molecular interactions of rhodomyrtone with FtsZ. Using molecular simulation, FtsZ conformational changes were observed in both (S)- and (R)-rhodomyrtone binding states, compared with the three natural states of FtsZ (ligand-free, GDP-, and GTP-binding states). Calculations of free binding energy showed a higher affinity of FtsZ to (S)-rhodomyrtone (−35.92 ± 0.36 kcal mol−1) than the GDP substrate (−23.47 ± 0.25 kcal mol−1) while less affinity was observed in the case of (R)-rhodomyrtone (−18.11 ± 0.11 kcal mol−1). In vitro experiments further revealed that rhodomyrtone reduced FtsZ polymerization by 36% and inhibited GTPase activity by up to 45%. However, the compound had no effect on FtsZ localization in Bacillus subtilis at inhibitory concentrations and cells also did not elongate after treatment. Higher concentrations of rhodomyrtone did affect localization of FtsZ and also affected localization of its membrane anchor proteins FtsA and SepF, showing that the compound did not specifically inhibit FtsZ but rather impaired multiple divisome proteins. Furthermore, a number of cells adopted a bean-like shape suggesting that rhodomyrtone possibly possesses further targets involved in cell envelope synthesis and/or maintenance.https://peerj.com/articles/2962.pdfRhodomyrtoneTubulin homologue FtsZCell divisionMolecular dynamics simulationBinding free energy |
| spellingShingle | Dennapa Saeloh Michaela Wenzel Thanyada Rungrotmongkol Leendert Willem Hamoen Varomyalin Tipmanee Supayang Piyawan Voravuthikunchai Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ PeerJ Rhodomyrtone Tubulin homologue FtsZ Cell division Molecular dynamics simulation Binding free energy |
| title | Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ |
| title_full | Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ |
| title_fullStr | Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ |
| title_full_unstemmed | Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ |
| title_short | Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ |
| title_sort | effects of rhodomyrtone on gram positive bacterial tubulin homologue ftsz |
| topic | Rhodomyrtone Tubulin homologue FtsZ Cell division Molecular dynamics simulation Binding free energy |
| url | https://peerj.com/articles/2962.pdf |
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