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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Autores principales: Binu Kundukad, Megan Schussman, Kaiyuan Yang, Thomas Seviour, Liang Yang, Scott A. Rice, Staffan Kjelleberg, Patrick S. Doyle
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/9b8e138e560d4001bbb139f09e7bce07
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
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