Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020
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| Online Access: | https://hdl.handle.net/1721.1/123439 |
| _version_ | 1811094384479830016 |
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| author | Romano, Keith P. Warrier, Thulasi Poulsen, Bradley E. Nguyen, Phuong H. Loftis, Alexander R. Saebi, Azin Pentelute, Bradley L. Hung, Deborah T |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Romano, Keith P. Warrier, Thulasi Poulsen, Bradley E. Nguyen, Phuong H. Loftis, Alexander R. Saebi, Azin Pentelute, Bradley L. Hung, Deborah T |
| author_sort | Romano, Keith P. |
| collection | MIT |
| description | Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene pmrB. Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding. |
| first_indexed | 2024-09-23T15:59:12Z |
| format | Article |
| id | mit-1721.1/123439 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:59:12Z |
| publishDate | 2020 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | mit-1721.1/1234392022-10-02T05:33:18Z Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa Romano, Keith P. Warrier, Thulasi Poulsen, Bradley E. Nguyen, Phuong H. Loftis, Alexander R. Saebi, Azin Pentelute, Bradley L. Hung, Deborah T Massachusetts Institute of Technology. Department of Chemistry Broad Institute of MIT and Harvard Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene pmrB. Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding. National Institutes of Health (U.S.) (Grant R01AI117043-04) 2020-01-14T16:45:36Z 2020-01-14T16:45:36Z 2019-06 2019-03 2020-01-02T19:25:10Z Article http://purl.org/eprint/type/JournalArticle 0066-4804 1098-6596 https://hdl.handle.net/1721.1/123439 Romano, Keith P. "Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa." Mechanisms of Resistance 63, 9 (August 2019): e00511-19 © 2019 The Authors en http://dx.doi.org/10.1128/aac.00511-19 Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Microbiology American Society for Microbiology |
| spellingShingle | Romano, Keith P. Warrier, Thulasi Poulsen, Bradley E. Nguyen, Phuong H. Loftis, Alexander R. Saebi, Azin Pentelute, Bradley L. Hung, Deborah T Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title | Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title_full | Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title_fullStr | Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title_full_unstemmed | Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title_short | Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa |
| title_sort | mutations in pmrb confer cross resistance between the lptd inhibitor pol7080 and colistin in pseudomonas aeruginosa |
| url | https://hdl.handle.net/1721.1/123439 |
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