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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
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Weak acids as an alternative anti-microbial therapy.

Binu Kundukad1, Gayathri Udayakumar2, Erin Grela3

  • 1BioSystems and Micromechanics (BioSyM) IRG, Singapore MIT Alliance for Research and Technology (SMART), Singapore.

Biofilm
|January 15, 2021
PubMed
Summary

Weak acids effectively eradicate biofilms by penetrating bacterial cells. N-acetyl cysteine (NAC) and other weak acids show broad-spectrum activity against antibiotic-resistant bacteria and biofilms, with potential for safe therapeutic applications.

Keywords:
BiofilmWeak acidspHpKa

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Area of Science:

  • Microbiology
  • Biochemistry
  • Antimicrobial Research

Background:

  • Biofilms pose a significant challenge in treating bacterial infections due to inherent resistance.
  • Weak acids can penetrate biofilm matrices and bacterial cell membranes.
  • Understanding optimal conditions for weak acid efficacy and safety is crucial for therapeutic and surface inactivation applications.

Purpose of the Study:

  • To investigate the efficacy of various weak acids in eradicating biofilms.
  • To determine the optimal conditions for weak acid activity against biofilms, including drug-resistant strains.
  • To assess the safety profile of weak acid drugs for potential clinical use.

Main Methods:

  • Compared the biofilm eradication efficacy of monoprotic (N-acetyl cysteine, acetic acid, formic acid) and triprotic (citric acid) weak acids.
  • Tested weak acid activity against biofilms of various bacterial species, including *Pseudomonas aeruginosa* (mucoid and antibiotic-resistant strains), *Klebsiella pneumoniae*, *Pseudomonas putida*, and *Staphylococcus aureus*.
  • Evaluated the effect of pH relative to the acid's pKa on bacterial killing.
  • Assessed the cytotoxicity of N-acetyl cysteine (NAC) on human cells.

Main Results:

  • Monoprotic weak acids eradicated biofilms when the pH was below their pKa, indicating no protection from the biofilm matrix.
  • Triprotic acids showed efficacy at pH < pKa1, but variable efficacy at pH between pKa1 and pKa2.
  • Weak acids demonstrated broad-spectrum activity against diverse bacteria, including antibiotic-resistant strains.
  • N-acetyl cysteine (NAC) showed potential for non-toxic bacterial killing of human cells when pH is near its pKa.

Conclusions:

  • Weak acids are effective broad-spectrum agents against biofilms, including antibiotic-resistant bacteria and persister cells.
  • The pH relative to the pKa is a critical factor determining weak acid efficacy.
  • Weak acid drugs like NAC offer a promising avenue for biofilm eradication with a favorable safety profile.