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Mechanistic action of weak acid drugs on biofilms

Author(s)
Kundukad, Binu; Yang, Kaiyuan; Seviour, Thomas; Yang, Liang; Rice, Scott A.; Kjelleberg, Staffan; Schussman, Megan K.; Doyle, Patrick S; ... Show more Show less
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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.
Date issued
2017-07
URI
http://hdl.handle.net/1721.1/113621
Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Chemical Engineering
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Kundukad, Binu et al. "Mechanistic action of weak acid drugs on biofilms." Scientific Reports 7 (July 2017): 4783 © 2017 The Author(s)
Version: Final published version
ISSN
2045-2322

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