Mechanisms of a Mycobacterium tuberculosis active peptide
Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understa...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/169738 |
| _version_ | 1811681706328981504 |
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| author | Rao, Komal Umashankar Li, Ping Welinder, Charlotte Tenland, Erik Gourdon, Pontus Sturegård, Erik Ho, James Chin Shing Godaly, Gabriela |
| author2 | Singapore Centre for Environmental Life Sciences and Engineering |
| author_facet | Singapore Centre for Environmental Life Sciences and Engineering Rao, Komal Umashankar Li, Ping Welinder, Charlotte Tenland, Erik Gourdon, Pontus Sturegård, Erik Ho, James Chin Shing Godaly, Gabriela |
| author_sort | Rao, Komal Umashankar |
| collection | NTU |
| description | Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis inner membranes induced tube-shaped membranous structures and massive vesicle formation, thus leading to bubbling cell death and ghost cell formation. Liposomal studies revealed that peptide insertion into inner membranes induced changes in the peptides' secondary structure and that the membranes were pulled such that they aggregated without permeabilization, suggesting that the peptide has a strong inner membrane affinity. Finally, the peptide targeted essential proteins in M. tuberculosis, such as 60 kDa chaperonins and elongation factor Tu, that are involved in mycolic acid synthesis and protein folding, which had an impact on bacterial proliferation. The observed multifaceted targeting provides additional support for the therapeutic potential of this peptide. |
| first_indexed | 2024-10-01T03:45:12Z |
| format | Journal Article |
| id | ntu-10356/169738 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:45:12Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1697382023-08-03T15:30:21Z Mechanisms of a Mycobacterium tuberculosis active peptide Rao, Komal Umashankar Li, Ping Welinder, Charlotte Tenland, Erik Gourdon, Pontus Sturegård, Erik Ho, James Chin Shing Godaly, Gabriela Singapore Centre for Environmental Life Sciences and Engineering Science::Biological sciences Mycobacterium Tuberculosis Antimicrobial Peptides Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis inner membranes induced tube-shaped membranous structures and massive vesicle formation, thus leading to bubbling cell death and ghost cell formation. Liposomal studies revealed that peptide insertion into inner membranes induced changes in the peptides' secondary structure and that the membranes were pulled such that they aggregated without permeabilization, suggesting that the peptide has a strong inner membrane affinity. Finally, the peptide targeted essential proteins in M. tuberculosis, such as 60 kDa chaperonins and elongation factor Tu, that are involved in mycolic acid synthesis and protein folding, which had an impact on bacterial proliferation. The observed multifaceted targeting provides additional support for the therapeutic potential of this peptide. Nanyang Technological University Published version This research was funded by the Swedish Heart–Lung Foundation and King Oscar II’s anniversary fund (20200378, 2021057422), Alfred Österlund Foundation, Royal Physiographic Society of Lund, and Swedish Research Council. JCSH is supported by the Provost Office, Nanyang Technological University, Singapore. 2023-08-01T07:15:27Z 2023-08-01T07:15:27Z 2023 Journal Article Rao, K. U., Li, P., Welinder, C., Tenland, E., Gourdon, P., Sturegård, E., Ho, J. C. S. & Godaly, G. (2023). Mechanisms of a Mycobacterium tuberculosis active peptide. Pharmaceutics, 15(2), 540-. https://dx.doi.org/10.3390/pharmaceutics15020540 1999-4923 https://hdl.handle.net/10356/169738 10.3390/pharmaceutics15020540 36839864 2-s2.0-85149137531 2 15 540 en Pharmaceutics © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Mycobacterium Tuberculosis Antimicrobial Peptides Rao, Komal Umashankar Li, Ping Welinder, Charlotte Tenland, Erik Gourdon, Pontus Sturegård, Erik Ho, James Chin Shing Godaly, Gabriela Mechanisms of a Mycobacterium tuberculosis active peptide |
| title | Mechanisms of a Mycobacterium tuberculosis active peptide |
| title_full | Mechanisms of a Mycobacterium tuberculosis active peptide |
| title_fullStr | Mechanisms of a Mycobacterium tuberculosis active peptide |
| title_full_unstemmed | Mechanisms of a Mycobacterium tuberculosis active peptide |
| title_short | Mechanisms of a Mycobacterium tuberculosis active peptide |
| title_sort | mechanisms of a mycobacterium tuberculosis active peptide |
| topic | Science::Biological sciences Mycobacterium Tuberculosis Antimicrobial Peptides |
| url | https://hdl.handle.net/10356/169738 |
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