A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice
The incidence of serious lung infections due to Mycobacterium abscessus, a worrying non-tuberculosis mycobacteria (NTM) species, is rising and has in some countries surpassed tuberculosis. NTM are ubiquitous in the environment and can cause serious lung infections in people who are immunocompromised...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2025
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| Online Access: | https://hdl.handle.net/10356/182470 |
| _version_ | 1826118015504089088 |
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| author | Si, Zhangyong Sun, Yan Tan, Chongyun Ooi, Ying Jie Li, Ming Raju, Cheerlavancha Shubi, Jamal Gan, Yunn-Hwen Zhu, Yabin Li, Peng Chan-Park, Mary B. Pethe, Kevin |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Si, Zhangyong Sun, Yan Tan, Chongyun Ooi, Ying Jie Li, Ming Raju, Cheerlavancha Shubi, Jamal Gan, Yunn-Hwen Zhu, Yabin Li, Peng Chan-Park, Mary B. Pethe, Kevin |
| author_sort | Si, Zhangyong |
| collection | NTU |
| description | The incidence of serious lung infections due to Mycobacterium abscessus, a worrying non-tuberculosis mycobacteria (NTM) species, is rising and has in some countries surpassed tuberculosis. NTM are ubiquitous in the environment and can cause serious lung infections in people who are immunocompromised or have pre-existing lung conditions. M. abscessus is intrinsically resistant to most antibiotics. Current treatments involve combination of three or more repurposed antibiotics with the treatment regimen lasting at least 12 months but producing unsatisfactory success rates of less than 50 %. Herein, we report an alternative strategy using a degradable polymer, specifically main-chain cationic carbonate-imidazolium-derived polymer (MCOP-1). MCOP-1 is a non-toxic agent active in a murine lung infection model. MCOP-1 also exhibits excellent efficacy against multi-drug resistant (MDR) ESKAPE bacteria. MCOP-1 damages bacterial membrane and DNA, and serial passaging does not rapidly elicit resistance. Its carbonate linkage is stable enough to allow MCOP-1 to remain intact for long enough to exert its bactericidal effect but is labile over longer time periods to degrade into non-toxic small molecules. These findings underscore the potential of degradable MCOP-1 as a promising therapeutic antimicrobial agent to address the growing incidence of recalcitrant infections due to M. abscessus and MDR ESKAPE bacteria. |
| first_indexed | 2025-03-09T12:04:10Z |
| format | Journal Article |
| id | ntu-10356/182470 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-03-09T12:04:10Z |
| publishDate | 2025 |
| record_format | dspace |
| spelling | ntu-10356/1824702025-02-04T02:29:58Z A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice Si, Zhangyong Sun, Yan Tan, Chongyun Ooi, Ying Jie Li, Ming Raju, Cheerlavancha Shubi, Jamal Gan, Yunn-Hwen Zhu, Yabin Li, Peng Chan-Park, Mary B. Pethe, Kevin Lee Kong Chian School of Medicine (LKCMedicine) School of Chemistry, Chemical Engineering and Biotechnology National Center for Infectious Diseases, Singapore Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) Medicine, Health and Life Sciences Bactericidal Mycobacterium abscessus The incidence of serious lung infections due to Mycobacterium abscessus, a worrying non-tuberculosis mycobacteria (NTM) species, is rising and has in some countries surpassed tuberculosis. NTM are ubiquitous in the environment and can cause serious lung infections in people who are immunocompromised or have pre-existing lung conditions. M. abscessus is intrinsically resistant to most antibiotics. Current treatments involve combination of three or more repurposed antibiotics with the treatment regimen lasting at least 12 months but producing unsatisfactory success rates of less than 50 %. Herein, we report an alternative strategy using a degradable polymer, specifically main-chain cationic carbonate-imidazolium-derived polymer (MCOP-1). MCOP-1 is a non-toxic agent active in a murine lung infection model. MCOP-1 also exhibits excellent efficacy against multi-drug resistant (MDR) ESKAPE bacteria. MCOP-1 damages bacterial membrane and DNA, and serial passaging does not rapidly elicit resistance. Its carbonate linkage is stable enough to allow MCOP-1 to remain intact for long enough to exert its bactericidal effect but is labile over longer time periods to degrade into non-toxic small molecules. These findings underscore the potential of degradable MCOP-1 as a promising therapeutic antimicrobial agent to address the growing incidence of recalcitrant infections due to M. abscessus and MDR ESKAPE bacteria. Ministry of Education (MOE) This work was funded and supported by the Singapore MOE Tier 3 grant (MOE2018-T3-1-003). 2025-02-04T02:29:58Z 2025-02-04T02:29:58Z 2025 Journal Article Si, Z., Sun, Y., Tan, C., Ooi, Y. J., Li, M., Raju, C., Shubi, J., Gan, Y., Zhu, Y., Li, P., Chan-Park, M. B. & Pethe, K. (2025). A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice. Biomaterials, 316, 123003-. https://dx.doi.org/10.1016/j.biomaterials.2024.123003 0142-9612 https://hdl.handle.net/10356/182470 10.1016/j.biomaterials.2024.123003 39709850 2-s2.0-85212587604 316 123003 en MOE2018-T3-1-003 Biomaterials © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. |
| spellingShingle | Medicine, Health and Life Sciences Bactericidal Mycobacterium abscessus Si, Zhangyong Sun, Yan Tan, Chongyun Ooi, Ying Jie Li, Ming Raju, Cheerlavancha Shubi, Jamal Gan, Yunn-Hwen Zhu, Yabin Li, Peng Chan-Park, Mary B. Pethe, Kevin A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title | A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title_full | A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title_fullStr | A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title_full_unstemmed | A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title_short | A cationic main-chain poly(carbonate-imidazolium) potent against Mycobacterium abscessus and other resistant bacteria in mice |
| title_sort | cationic main chain poly carbonate imidazolium potent against mycobacterium abscessus and other resistant bacteria in mice |
| topic | Medicine, Health and Life Sciences Bactericidal Mycobacterium abscessus |
| url | https://hdl.handle.net/10356/182470 |
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