Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations.

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  • Author(s): Lekhan A;Lekhan A; Turner RJ; Turner RJ
  • Source:
    Microbiology spectrum [Microbiol Spectr] 2024 Oct 03; Vol. 12 (10), pp. e0104724. Date of Electronic Publication: 2024 Aug 20.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : ASM Press, 2013-
    • Subject Terms:
      Quaternary Ammonium Compounds*/pharmacology ; Quaternary Ammonium Compounds*/chemistry ; Drug Synergism* ; Microbial Sensitivity Tests* ; Anti-Bacterial Agents*/pharmacology ; Anti-Bacterial Agents*/chemistry ; Pseudomonas aeruginosa*/drug effects ; Pseudomonas aeruginosa*/growth & development ; Biofilms*/drug effects ; Escherichia coli*/drug effects ; Escherichia coli*/growth & development; Metals/chemistry ; Metals/pharmacology ; Benzalkonium Compounds/pharmacology ; Benzalkonium Compounds/chemistry ; Cetrimonium/chemistry ; Anti-Infective Agents/pharmacology ; Anti-Infective Agents/chemistry ; Ions/chemistry ; Ions/pharmacology
    • Abstract:
      Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor-the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used.
      Importance: We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.
      Competing Interests: The authors declare no conflict of interest.
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    • Grant Information:
      Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)
    • Contributed Indexing:
      Keywords: antimicrobial mixtures; biofilm prevention; checkerboard assay; metal-based antimicrobials; quaternary ammonium compounds; synergy
    • Accession Number:
      0 (Quaternary Ammonium Compounds)
      0 (Anti-Bacterial Agents)
      0 (Metals)
      0 (Benzalkonium Compounds)
      Z7FF1XKL7A (Cetrimonium)
      0 (Anti-Infective Agents)
      0 (Ions)
    • Publication Date:
      Date Created: 20240820 Date Completed: 20241004 Latest Revision: 20241005
    • Publication Date:
      20241005
    • Accession Number:
      PMC11448152
    • Accession Number:
      10.1128/spectrum.01047-24
    • Accession Number:
      39162494