Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action
Extracellular histones play a dual role—antimicrobial and cytotoxic—in host defense. In this study, we evaluated the antimicrobial and cytotoxic activities of histone H3 and identified the responsible molecular regions for these properties. Broth microdilution assays indicated that histone H3 exhibi...
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MDPI AG
2022-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/9/1240 |
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| author | Yuri Tanaka Nanako Yamanaka Izumi Koyano Itaru Hasunuma Tetsuya Kobayashi Sakae Kikuyama Shawichi Iwamuro |
| author_facet | Yuri Tanaka Nanako Yamanaka Izumi Koyano Itaru Hasunuma Tetsuya Kobayashi Sakae Kikuyama Shawichi Iwamuro |
| author_sort | Yuri Tanaka |
| collection | DOAJ |
| description | Extracellular histones play a dual role—antimicrobial and cytotoxic—in host defense. In this study, we evaluated the antimicrobial and cytotoxic activities of histone H3 and identified the responsible molecular regions for these properties. Broth microdilution assays indicated that histone H3 exhibits growth inhibitory activity against not only Gram-negative and -positive bacteria but also fungi. Observations under scanning electron microscopy (SEM) revealed that histone H3 induced morphological abnormalities on the cell surface of a wide range of reference pathogens. MTT assays and SEM observations indicated that histone H3 has strong cytotoxic and cell lytic effects on mammalian normal, immortal, and tumor cell lines. Assays using synthetic peptides corresponding to fragments 1–34 (H3DP1), 35–68 (H3DP2), 69–102 (H3DP3), and 103–135 (H3DP4) of histone H3 molecule demonstrated that its antimicrobial activity and cytotoxicity are elicited by the H3DP2 and H3DP3 protein regions, respectively. Enzyme-linked endotoxin binding assays indicated that histones H3 and H3DP1, H3DP2, and H3DP4, but not H3DP3, exhibited high affinities toward lipopolysaccharide and lipoteichoic acid. Our findings are expected to contribute to the development of new histone H3-based peptide antibiotics that are not cytotoxic. |
| first_indexed | 2024-03-10T00:55:20Z |
| format | Article |
| id | doaj.art-f946492d18344069aa0ae4275137e66e |
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| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T00:55:20Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-f946492d18344069aa0ae4275137e66e2023-11-23T14:45:24ZengMDPI AGAntibiotics2079-63822022-09-01119124010.3390/antibiotics11091240Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of ActionYuri Tanaka0Nanako Yamanaka1Izumi Koyano2Itaru Hasunuma3Tetsuya Kobayashi4Sakae Kikuyama5Shawichi Iwamuro6Department of Biology, Faculty of Science, Toho University, Chiba 274-8510, JapanDepartment of Biology, Faculty of Science, Toho University, Chiba 274-8510, JapanDepartment of Biology, Faculty of Science, Toho University, Chiba 274-8510, JapanDepartment of Biology, Faculty of Science, Toho University, Chiba 274-8510, JapanDivision of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanDepartment of Biology, Faculty of Education and Integrated Arts and Sciences, Center for Advanced Biomedical Sciences, Waseda University, Tokyo 162-8480, JapanDepartment of Biology, Faculty of Science, Toho University, Chiba 274-8510, JapanExtracellular histones play a dual role—antimicrobial and cytotoxic—in host defense. In this study, we evaluated the antimicrobial and cytotoxic activities of histone H3 and identified the responsible molecular regions for these properties. Broth microdilution assays indicated that histone H3 exhibits growth inhibitory activity against not only Gram-negative and -positive bacteria but also fungi. Observations under scanning electron microscopy (SEM) revealed that histone H3 induced morphological abnormalities on the cell surface of a wide range of reference pathogens. MTT assays and SEM observations indicated that histone H3 has strong cytotoxic and cell lytic effects on mammalian normal, immortal, and tumor cell lines. Assays using synthetic peptides corresponding to fragments 1–34 (H3DP1), 35–68 (H3DP2), 69–102 (H3DP3), and 103–135 (H3DP4) of histone H3 molecule demonstrated that its antimicrobial activity and cytotoxicity are elicited by the H3DP2 and H3DP3 protein regions, respectively. Enzyme-linked endotoxin binding assays indicated that histones H3 and H3DP1, H3DP2, and H3DP4, but not H3DP3, exhibited high affinities toward lipopolysaccharide and lipoteichoic acid. Our findings are expected to contribute to the development of new histone H3-based peptide antibiotics that are not cytotoxic.https://www.mdpi.com/2079-6382/11/9/1240histone H3antimicrobial activitycytotoxicitycell membrane destructionELEBA |
| spellingShingle | Yuri Tanaka Nanako Yamanaka Izumi Koyano Itaru Hasunuma Tetsuya Kobayashi Sakae Kikuyama Shawichi Iwamuro Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action Antibiotics histone H3 antimicrobial activity cytotoxicity cell membrane destruction ELEBA |
| title | Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action |
| title_full | Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action |
| title_fullStr | Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action |
| title_full_unstemmed | Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action |
| title_short | Dual Roles of Extracellular Histone H3 in Host Defense: Its Differential Regions Responsible for Antimicrobial and Cytotoxic Properties and Their Modes of Action |
| title_sort | dual roles of extracellular histone h3 in host defense its differential regions responsible for antimicrobial and cytotoxic properties and their modes of action |
| topic | histone H3 antimicrobial activity cytotoxicity cell membrane destruction ELEBA |
| url | https://www.mdpi.com/2079-6382/11/9/1240 |
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