Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination
Host defense cationic Antimicrobial Peptides (AMPs) can kill microorganisms including bacteria, viruses and fungi using various modes of action. The negatively charged bacterial membranes serve as a key target for many AMPs. Bacterial cell death by membrane permeabilization has been well perceived....
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/87993 http://hdl.handle.net/10220/44511 |
| _version_ | 1811693555089932288 |
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| author | Sinha, Sheetal Zheng, Liangzhen Mu, Yuguang Ng, Wun Jern Bhattacharjya, Surajit |
| author2 | School of Civil and Environmental Engineering |
| author_facet | School of Civil and Environmental Engineering Sinha, Sheetal Zheng, Liangzhen Mu, Yuguang Ng, Wun Jern Bhattacharjya, Surajit |
| author_sort | Sinha, Sheetal |
| collection | NTU |
| description | Host defense cationic Antimicrobial Peptides (AMPs) can kill microorganisms including bacteria, viruses and fungi using various modes of action. The negatively charged bacterial membranes serve as a key target for many AMPs. Bacterial cell death by membrane permeabilization has been well perceived. A number of cationic AMPs kill bacteria by cell agglutination which is a distinctly different mode of action compared to membrane pore formation. However, mechanism of cell agglutinating AMPs is poorly understood. The outer membrane lipopolysaccharide (LPS) or the cell-wall peptidoglycans are targeted by AMPs as a key step in agglutination process. Here, we report the first atomic-resolution structure of thanatin, a cell agglutinating AMP, in complex with LPS micelle by solution NMR. The structure of thanatin in complex with LPS, revealed four stranded antiparallel β-sheet in a ‘head-tail’ dimeric topology. By contrast, thanatin in free solution assumed an antiparallel β-hairpin conformation. Dimeric structure of thanatin displayed higher hydrophobicity and cationicity with sites of LPS interactions. MD simulations and biophysical interactions analyses provided mode of LPS recognition and perturbation of LPS micelle structures. Mechanistic insights of bacterial cell agglutination obtained in this study can be utilized to develop antibiotics of alternative mode of action. |
| first_indexed | 2024-10-01T06:53:32Z |
| format | Journal Article |
| id | ntu-10356/87993 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:53:32Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/879932020-09-26T22:01:31Z Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination Sinha, Sheetal Zheng, Liangzhen Mu, Yuguang Ng, Wun Jern Bhattacharjya, Surajit School of Civil and Environmental Engineering School of Biological Sciences Interdisciplinary Graduate School (IGS) Nanyang Environment and Water Research Institute Thanatin Bacterial Cell Agglutination Host defense cationic Antimicrobial Peptides (AMPs) can kill microorganisms including bacteria, viruses and fungi using various modes of action. The negatively charged bacterial membranes serve as a key target for many AMPs. Bacterial cell death by membrane permeabilization has been well perceived. A number of cationic AMPs kill bacteria by cell agglutination which is a distinctly different mode of action compared to membrane pore formation. However, mechanism of cell agglutinating AMPs is poorly understood. The outer membrane lipopolysaccharide (LPS) or the cell-wall peptidoglycans are targeted by AMPs as a key step in agglutination process. Here, we report the first atomic-resolution structure of thanatin, a cell agglutinating AMP, in complex with LPS micelle by solution NMR. The structure of thanatin in complex with LPS, revealed four stranded antiparallel β-sheet in a ‘head-tail’ dimeric topology. By contrast, thanatin in free solution assumed an antiparallel β-hairpin conformation. Dimeric structure of thanatin displayed higher hydrophobicity and cationicity with sites of LPS interactions. MD simulations and biophysical interactions analyses provided mode of LPS recognition and perturbation of LPS micelle structures. Mechanistic insights of bacterial cell agglutination obtained in this study can be utilized to develop antibiotics of alternative mode of action. MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2018-03-06T03:09:50Z 2019-12-06T16:53:40Z 2018-03-06T03:09:50Z 2019-12-06T16:53:40Z 2017 Journal Article Sinha, S., Zheng, L., Mu, Y., Ng, W. J., & Bhattacharjya, S. (2017). Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination. Scientific Reports, 7(1), 17795-. 2045-2322 https://hdl.handle.net/10356/87993 http://hdl.handle.net/10220/44511 10.1038/s41598-017-18102-6 en Scientific Reports © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 13 p. application/pdf |
| spellingShingle | Thanatin Bacterial Cell Agglutination Sinha, Sheetal Zheng, Liangzhen Mu, Yuguang Ng, Wun Jern Bhattacharjya, Surajit Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title | Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title_full | Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title_fullStr | Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title_full_unstemmed | Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title_short | Structure and Interactions of A Host Defense Antimicrobial Peptide Thanatin in Lipopolysaccharide Micelles Reveal Mechanism of Bacterial Cell Agglutination |
| title_sort | structure and interactions of a host defense antimicrobial peptide thanatin in lipopolysaccharide micelles reveal mechanism of bacterial cell agglutination |
| topic | Thanatin Bacterial Cell Agglutination |
| url | https://hdl.handle.net/10356/87993 http://hdl.handle.net/10220/44511 |
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