Mechanistic action of weak acid drugs on biofilms
Selective permeability of a biofilm matrix to some drugs has resulted in the development of drug tolerant bacteria. Here we studied the efficacy of a weak organic acid drug, N-acetyl-L-cysteine (NAC), on the eradication of biofilms formed by the mucoid strain of Pseudomonas aeruginosa and investigat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/113621 https://orcid.org/0000-0003-2147-9172 |
| _version_ | 1826190583563026432 |
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| author | Kundukad, Binu Yang, Kaiyuan Seviour, Thomas Yang, Liang Rice, Scott A. Kjelleberg, Staffan Schussman, Megan K. Doyle, Patrick S |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Kundukad, Binu Yang, Kaiyuan Seviour, Thomas Yang, Liang Rice, Scott A. Kjelleberg, Staffan Schussman, Megan K. Doyle, Patrick S |
| author_sort | Kundukad, Binu |
| collection | MIT |
| description | Selective permeability of a biofilm matrix to some drugs has resulted in the development of drug tolerant bacteria. Here we studied the efficacy of a weak organic acid drug, N-acetyl-L-cysteine (NAC), on the eradication of biofilms formed by the mucoid strain of Pseudomonas aeruginosa and investigated the commonality of this drug with that of acetic acid. We showed that NAC and acetic acid at pH < pKa can penetrate the matrix and eventually kill 100% of the bacteria embedded in the biofilm. Once the bacteria are killed, the microcolonies swell in size and passively shed bacteria, suggesting that the bacteria act as crosslinkers within the extracellular matrix. Despite shedding of the bacteria, the remnant matrix remains intact and behaves as a pH-responsive hydrogel. These studies not only have implications for drug design but also offer a route to generate robust soft matter materials. |
| first_indexed | 2024-09-23T08:42:34Z |
| format | Article |
| id | mit-1721.1/113621 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:42:34Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1136212022-09-23T14:03:03Z Mechanistic action of weak acid drugs on biofilms Kundukad, Binu Yang, Kaiyuan Seviour, Thomas Yang, Liang Rice, Scott A. Kjelleberg, Staffan Schussman, Megan K. Doyle, Patrick S Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Chemical Engineering Schussman, Megan K. Doyle, Patrick S Selective permeability of a biofilm matrix to some drugs has resulted in the development of drug tolerant bacteria. Here we studied the efficacy of a weak organic acid drug, N-acetyl-L-cysteine (NAC), on the eradication of biofilms formed by the mucoid strain of Pseudomonas aeruginosa and investigated the commonality of this drug with that of acetic acid. We showed that NAC and acetic acid at pH < pKa can penetrate the matrix and eventually kill 100% of the bacteria embedded in the biofilm. Once the bacteria are killed, the microcolonies swell in size and passively shed bacteria, suggesting that the bacteria act as crosslinkers within the extracellular matrix. Despite shedding of the bacteria, the remnant matrix remains intact and behaves as a pH-responsive hydrogel. These studies not only have implications for drug design but also offer a route to generate robust soft matter materials. 2018-02-13T15:03:13Z 2018-02-13T15:03:13Z 2017-07 2017-03 2018-02-09T17:25:24Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/113621 Kundukad, Binu et al. "Mechanistic action of weak acid drugs on biofilms." Scientific Reports 7 (July 2017): 4783 © 2017 The Author(s) https://orcid.org/0000-0003-2147-9172 http://dx.doi.org/10.1038/S41598-017-05178-3 Scientific Reports Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group |
| spellingShingle | Kundukad, Binu Yang, Kaiyuan Seviour, Thomas Yang, Liang Rice, Scott A. Kjelleberg, Staffan Schussman, Megan K. Doyle, Patrick S Mechanistic action of weak acid drugs on biofilms |
| title | Mechanistic action of weak acid drugs on biofilms |
| title_full | Mechanistic action of weak acid drugs on biofilms |
| title_fullStr | Mechanistic action of weak acid drugs on biofilms |
| title_full_unstemmed | Mechanistic action of weak acid drugs on biofilms |
| title_short | Mechanistic action of weak acid drugs on biofilms |
| title_sort | mechanistic action of weak acid drugs on biofilms |
| url | http://hdl.handle.net/1721.1/113621 https://orcid.org/0000-0003-2147-9172 |
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