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.
Highlights
Biofilms are colonies of bacteria held together by a self-secreted extracellular polymeric substance (EPS) called the matrix
Macrolide antibiotics have shown to be effective against chronic cystic fibrosis lung disease caused by mucoid P. aeruginosa as they play a role in disrupting the matrix[19]
We show that NAC and acetic acid at pH < pKa can penetrate the matrix of the biofilm and kill 100% of the bacteria embedded in the matrix
Summary
Biofilms are colonies of bacteria held together by a self-secreted extracellular polymeric substance (EPS) called the matrix. Microrheology studies have identified the contribution of different polysaccharides, namely Psl and Pel, on the viscoelastic properties of biofilm[7]. The antibiotics can be inactivated by binding to the matrix or reacting with the matrix, which inhibit the antibiotics from reaching the depth of the biofilm microcolonies This diffusion-reaction interaction of the antibiotics is responsible for the prevention of some of the antibiotics from penetrating the biofilm. Ciprofloxacin and gluteraldehyde have been shown to weaken the material properties of P. aeruginosa biofilms[20]. Chemicals such as bismuth dimercaprol caused a reduction in polysaccharide production it was not effective in killing bacteria[21]. It becomes necessary to explore the possibility of (i) non-antibiotic drugs (ii) drugs that could diffuse through the matrix without the need of degrading the matrix
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