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...

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Bibliographic Details
Main Authors: Kundukad, Binu, Schussman, Megan, Yang, Kaiyuan, Seviour, Thomas, Yang, Liang, Rice, Scott A., Kjelleberg, Staffan, Doyle, Patrick S.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/88068
http://hdl.handle.net/10220/45622
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.