Weak acids as an alternative anti-microbial therapy
Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to b...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/147521 |
| _version_ | 1811693600215400448 |
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| author | Kundukad, Binu Udayakumar, Gayathri Grela, Erin Kaur, Dhamanpreet Rice, Scott A. Kjelleberg, Staffan Doyle, Patrick |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Kundukad, Binu Udayakumar, Gayathri Grela, Erin Kaur, Dhamanpreet Rice, Scott A. Kjelleberg, Staffan Doyle, Patrick |
| author_sort | Kundukad, Binu |
| collection | NTU |
| description | Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to be understood for their application to treat infections or to inactivate biofilms on hard surfaces. Here, we investigate the efficacy and optimum conditions at which weak acids can eradicate biofilms. We compared the efficacy of various mono and triprotic weak acids such as N-acetyl cysteine (NAC), acetic acid, formic acid and citric acid, in eradicating biofilms. We found that monoprotic weak acids/acid drugs can kill mucoid P. aeruginosa mucA biofilm bacteria provided the pH is less than their pKa, demonstrating that the extracellular biofilm matrix does not protect the bacteria from the activity of the weak acids. Triprotic acids, such as citric acid, kill biofilm bacteria at pH < pKa1. However, at a pH between pKa1 and pKa2, citric acid is effective in killing the bacteria at the core of biofilm microcolonies but does not kill the bacteria on the periphery. The efficacy of a monoprotic weak acid (NAC) and triprotic weak acid (citric acid) were tested on biofilms formed by Klebsiella pneumoniae KP1, Pseudomonas putida OUS82, Staphylococcus aureus 15981, P. aeruginosa DK1-NH57388A, a mucoid cystic fibrosis isolate and P. aeruginosa PA_D25, an antibiotic resistant strain. We showed that weak acids have a broad spectrum of activity against a wide range of bacteria, including antibiotic resistant bacteria. Further, we showed that a weak acid drug, NAC, can kill bacteria without being toxic to human cells, if its pH is maintained close to its pKa. Thus weak acids/weak acid drugs target antibiotic resistant bacteria and eradicate the persister cells in biofilms which are tolerant to other conventional methods of biofilm eradication. |
| first_indexed | 2024-10-01T06:54:15Z |
| format | Journal Article |
| id | ntu-10356/147521 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:54:15Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1475212021-04-10T20:11:47Z Weak acids as an alternative anti-microbial therapy Kundukad, Binu Udayakumar, Gayathri Grela, Erin Kaur, Dhamanpreet Rice, Scott A. Kjelleberg, Staffan Doyle, Patrick School of Biological Sciences Singapore Centre for Environmental Life Sciences and Engineering Science::Biological sciences Biofilm Weak Acids Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to be understood for their application to treat infections or to inactivate biofilms on hard surfaces. Here, we investigate the efficacy and optimum conditions at which weak acids can eradicate biofilms. We compared the efficacy of various mono and triprotic weak acids such as N-acetyl cysteine (NAC), acetic acid, formic acid and citric acid, in eradicating biofilms. We found that monoprotic weak acids/acid drugs can kill mucoid P. aeruginosa mucA biofilm bacteria provided the pH is less than their pKa, demonstrating that the extracellular biofilm matrix does not protect the bacteria from the activity of the weak acids. Triprotic acids, such as citric acid, kill biofilm bacteria at pH < pKa1. However, at a pH between pKa1 and pKa2, citric acid is effective in killing the bacteria at the core of biofilm microcolonies but does not kill the bacteria on the periphery. The efficacy of a monoprotic weak acid (NAC) and triprotic weak acid (citric acid) were tested on biofilms formed by Klebsiella pneumoniae KP1, Pseudomonas putida OUS82, Staphylococcus aureus 15981, P. aeruginosa DK1-NH57388A, a mucoid cystic fibrosis isolate and P. aeruginosa PA_D25, an antibiotic resistant strain. We showed that weak acids have a broad spectrum of activity against a wide range of bacteria, including antibiotic resistant bacteria. Further, we showed that a weak acid drug, NAC, can kill bacteria without being toxic to human cells, if its pH is maintained close to its pKa. Thus weak acids/weak acid drugs target antibiotic resistant bacteria and eradicate the persister cells in biofilms which are tolerant to other conventional methods of biofilm eradication. Ministry of Education (MOE) National Research Foundation (NRF) Published version This research was supported by the National Research Foundation, Singapore through the Singapore MIT Alliance for Research and Technology’s (SMART) BioSystems and Micromechanics (BioSyM) IRG research program and the National Science Foundation, USA. We also acknowledge support from the Singapore National Research Foundation and Ministry of Education, Singpaore under the Research Centre of Excellence program. 2021-04-08T02:07:44Z 2021-04-08T02:07:44Z 2020 Journal Article Kundukad, B., Udayakumar, G., Grela, E., Kaur, D., Rice, S. A., Kjelleberg, S. & Doyle, P. (2020). Weak acids as an alternative anti-microbial therapy. Biofilm, 2, 100019-. https://dx.doi.org/10.1016/j.bioflm.2020.100019 2590-2075 0000-0002-3301-5431 https://hdl.handle.net/10356/147521 10.1016/j.bioflm.2020.100019 2 100019 en Biofilm © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Biofilm Weak Acids Kundukad, Binu Udayakumar, Gayathri Grela, Erin Kaur, Dhamanpreet Rice, Scott A. Kjelleberg, Staffan Doyle, Patrick Weak acids as an alternative anti-microbial therapy |
| title | Weak acids as an alternative anti-microbial therapy |
| title_full | Weak acids as an alternative anti-microbial therapy |
| title_fullStr | Weak acids as an alternative anti-microbial therapy |
| title_full_unstemmed | Weak acids as an alternative anti-microbial therapy |
| title_short | Weak acids as an alternative anti-microbial therapy |
| title_sort | weak acids as an alternative anti microbial therapy |
| topic | Science::Biological sciences Biofilm Weak Acids |
| url | https://hdl.handle.net/10356/147521 |
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