Mechanistic action of weak acid drugs on biofilms
Abstract 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 i...
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Nature Portfolio
2017
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oai:doaj.org-article:9b8e138e560d4001bbb139f09e7bce072021-12-02T12:32:59ZMechanistic action of weak acid drugs on biofilms10.1038/s41598-017-05178-32045-2322https://doaj.org/article/9b8e138e560d4001bbb139f09e7bce072017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05178-3https://doaj.org/toc/2045-2322Abstract 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.Binu KundukadMegan SchussmanKaiyuan YangThomas SeviourLiang YangScott A. RiceStaffan KjellebergPatrick S. DoyleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Binu Kundukad Megan Schussman Kaiyuan Yang Thomas Seviour Liang Yang Scott A. Rice Staffan Kjelleberg Patrick S. Doyle Mechanistic action of weak acid drugs on biofilms |
description |
Abstract 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. |
format |
article |
author |
Binu Kundukad Megan Schussman Kaiyuan Yang Thomas Seviour Liang Yang Scott A. Rice Staffan Kjelleberg Patrick S. Doyle |
author_facet |
Binu Kundukad Megan Schussman Kaiyuan Yang Thomas Seviour Liang Yang Scott A. Rice Staffan Kjelleberg Patrick S. Doyle |
author_sort |
Binu Kundukad |
title |
Mechanistic action of weak acid drugs on biofilms |
title_short |
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_sort |
mechanistic action of weak acid drugs on biofilms |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/9b8e138e560d4001bbb139f09e7bce07 |
work_keys_str_mv |
AT binukundukad mechanisticactionofweakaciddrugsonbiofilms AT meganschussman mechanisticactionofweakaciddrugsonbiofilms AT kaiyuanyang mechanisticactionofweakaciddrugsonbiofilms AT thomasseviour mechanisticactionofweakaciddrugsonbiofilms AT liangyang mechanisticactionofweakaciddrugsonbiofilms AT scottarice mechanisticactionofweakaciddrugsonbiofilms AT staffankjelleberg mechanisticactionofweakaciddrugsonbiofilms AT patricksdoyle mechanisticactionofweakaciddrugsonbiofilms |
_version_ |
1718393935310618624 |