Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria
Antibiotic resistance is a rapidly evolving problem that is not being adequately met by new antimicrobial drugs. Thus, there is a pressing need for effective antibacterial therapies that can be adapted against antibiotic-resistant bacteria. Here, we engineered synthetic bacteriophage to combat antib...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Institute of Electrical and Electronics Engineers
2010
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| Online Access: | http://hdl.handle.net/1721.1/59963 https://orcid.org/0000-0002-9999-6690 |
| _version_ | 1826192883221266432 |
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| author | Lu, Timothy K. Collins, James J. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Lu, Timothy K. Collins, James J. |
| author_sort | Lu, Timothy K. |
| collection | MIT |
| description | Antibiotic resistance is a rapidly evolving problem that is not being adequately met by new antimicrobial drugs. Thus, there is a pressing need for effective antibacterial therapies that can be adapted against antibiotic-resistant bacteria. Here, we engineered synthetic bacteriophage to combat antibiotic-resistant bacteria by overexpressing proteins and attacking gene networks which are not directly targeted by antibiotics. By suppressing the SOS network, our engineered phage enhance bacterial killing by quinolone antibiotics by several orders of magnitude in vitro and significantly increase the survival of infected mice in vivo. Our synthetic phage design can be extended to target non-SOS gene networks and overexpress multiple factors to produce additional effective antibiotic adjuvants. In addition, our synthetic phage act as strong adjuvants for other bactericidal antibiotics, improve the killing of antibiotic-resistant bacteria, and reduce the number of antibiotic-resistant bacteria that arise from antibiotic-treated populations. This work establishes a novel synthetic biology platform for translating identified targets into effective antibiotic adjuvants. |
| first_indexed | 2024-09-23T09:30:38Z |
| format | Article |
| id | mit-1721.1/59963 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:30:38Z |
| publishDate | 2010 |
| publisher | Institute of Electrical and Electronics Engineers |
| record_format | dspace |
| spelling | mit-1721.1/599632022-09-26T11:53:31Z Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria Lu, Timothy K. Collins, James J. Harvard University--MIT Division of Health Sciences and Technology Lu, Timothy K. Lu, Timothy K. Collins, James J. Antibiotic resistance is a rapidly evolving problem that is not being adequately met by new antimicrobial drugs. Thus, there is a pressing need for effective antibacterial therapies that can be adapted against antibiotic-resistant bacteria. Here, we engineered synthetic bacteriophage to combat antibiotic-resistant bacteria by overexpressing proteins and attacking gene networks which are not directly targeted by antibiotics. By suppressing the SOS network, our engineered phage enhance bacterial killing by quinolone antibiotics by several orders of magnitude in vitro and significantly increase the survival of infected mice in vivo. Our synthetic phage design can be extended to target non-SOS gene networks and overexpress multiple factors to produce additional effective antibiotic adjuvants. In addition, our synthetic phage act as strong adjuvants for other bactericidal antibiotics, improve the killing of antibiotic-resistant bacteria, and reduce the number of antibiotic-resistant bacteria that arise from antibiotic-treated populations. This work establishes a novel synthetic biology platform for translating identified targets into effective antibiotic adjuvants. 2010-11-10T20:00:52Z 2010-11-10T20:00:52Z 2009-05 2009-04 Article http://purl.org/eprint/type/ConferencePaper 978-1-4244-4362-8 INSPEC Accession Number: 10684163 http://hdl.handle.net/1721.1/59963 Lu, T.K., and J.J. Collins. “Engineering synthetic bacteriophage to combat antibiotic-resistant bacteria.” Bioengineering Conference, 2009 IEEE 35th Annual Northeast. 2009. 1-2. © Copyright 2010 IEEE https://orcid.org/0000-0002-9999-6690 en_US http://dx.doi.org/10.1109/NEBC.2009.4967831 Proceedings of the IEEE 35th Annual Northeast Bioengineering Conference, 2009 Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Institute of Electrical and Electronics Engineers IEEE |
| spellingShingle | Lu, Timothy K. Collins, James J. Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title | Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title_full | Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title_fullStr | Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title_full_unstemmed | Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title_short | Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria |
| title_sort | engineering synthetic bacteriophage to combat antibiotic resistant bacteria |
| url | http://hdl.handle.net/1721.1/59963 https://orcid.org/0000-0002-9999-6690 |
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