Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens
Abstract CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targetin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-37789-y |
| _version_ | 1797845890537357312 |
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| author | Rui Wang Xian Shu Huiwei Zhao Qiong Xue Chao Liu Aici Wu Feiyue Cheng Lingyun Wang Yihan Zhang Jie Feng Nannan Wu Ming Li |
| author_facet | Rui Wang Xian Shu Huiwei Zhao Qiong Xue Chao Liu Aici Wu Feiyue Cheng Lingyun Wang Yihan Zhang Jie Feng Nannan Wu Ming Li |
| author_sort | Rui Wang |
| collection | DOAJ |
| description | Abstract CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to ‘ATTACK’ MDR pathogens. |
| first_indexed | 2024-04-09T17:46:17Z |
| format | Article |
| id | doaj.art-9af6f50038e3452486b995a0d6ccf7c5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T17:46:17Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9af6f50038e3452486b995a0d6ccf7c52023-04-16T11:18:52ZengNature PortfolioNature Communications2041-17232023-04-0114111310.1038/s41467-023-37789-yAssociate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogensRui Wang0Xian Shu1Huiwei Zhao2Qiong Xue3Chao Liu4Aici Wu5Feiyue Cheng6Lingyun Wang7Yihan Zhang8Jie Feng9Nannan Wu10Ming Li11CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Science, University of Chinese Academy of SciencesShanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan UniversityCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of SciencesAbstract CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to ‘ATTACK’ MDR pathogens.https://doi.org/10.1038/s41467-023-37789-y |
| spellingShingle | Rui Wang Xian Shu Huiwei Zhao Qiong Xue Chao Liu Aici Wu Feiyue Cheng Lingyun Wang Yihan Zhang Jie Feng Nannan Wu Ming Li Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens Nature Communications |
| title | Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens |
| title_full | Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens |
| title_fullStr | Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens |
| title_full_unstemmed | Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens |
| title_short | Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens |
| title_sort | associate toxin antitoxin with crispr cas to kill multidrug resistant pathogens |
| url | https://doi.org/10.1038/s41467-023-37789-y |
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