The Potential Antimicrobial Action of Human Mucin 7 15-Mer Peptide and Its Metal Complexes
Anna Janicka-Kłos1, Hanna Czapor-Irzabek2, Tomasz Janek3
1Department of Inorganic Chemistry, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Abstract:
Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (Enterococcus faecalis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.
Insights
Mucin 7 (MUC7) peptide fragments show antimicrobial activity. Metal ions like copper and zinc influence this activity, with implications for understanding how these peptides fight bacteria and fungi.
Area of Science:
- Biochemistry
- Microbiology
- Immunology
Background:
- Human salivary Mucin 7 (MUC7) is a protein integral to the innate immune system.
- MUC7 fragments possess antimicrobial properties against bacteria and fungi, though their precise mechanism remains elusive.
- Some antimicrobial peptides (AMPs) necessitate divalent metal ions for optimal activity.
Purpose of the Study:
- To investigate the antimicrobial activity of three MUC7-derived peptides and their complexes with Cu(II) and Zn(II) ions.
- To correlate antimicrobial efficacy with peptide lipophilicity and metal ion coordination.
- To elucidate the complex formation and stability of MUC7 peptides with Cu(II) and Zn(II) in a physiological pH range.
Main Methods:
- Synthesis and characterization of three 15-mer MUC7 peptides with varying histidine residues.
- Antimicrobial susceptibility testing against Gram-positive bacteria (Enterococcus faecalis, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and fungi (Candida albicans).
- Coordination and thermodynamic studies using potentiometry, UV-Vis, and Circular Dichroism (CD) spectroscopy.
Main Results:
- All three MUC7 peptides, both alone and complexed with Cu(II) and Zn(II), exhibited antimicrobial activity.
- Complexation with metal ions influenced peptide activity, with results correlating with lipophilicity.
- Potentiometry, UV-Vis, and CD studies confirmed the formation of predominantly mononuclear complexes in solution with varying stability across the physiological pH range.
Conclusions:
- MUC7 peptides, particularly when complexed with divalent metal ions like Cu(II) and Zn(II), demonstrate significant antimicrobial potential.
- Metal ion coordination plays a crucial role in modulating the antimicrobial activity of these salivary peptide fragments.
- The findings contribute to understanding the mechanism of action of MUC7-derived antimicrobial peptides and their interaction with metal ions.
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