The Potential Antimicrobial Action of Human Mucin 7 15-Mer Peptide and Its Metal Complexes

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.

Exploring the Correlation between Salivary Spinnbarkeit and Caries Scores

“…Though both mucins play a role in defence against bacteria, MUC7 achieves this by binding to oral pathogens, while MUC5B forms a bacteria-repellent layer on oral surfaces [37,38]. In addition, an antimicrobial 15-mer peptide may be released upon proteolytic degradation of MUC7 [39]. Some studies demonstrate that increased salivary viscosity is a risk factor for dental caries [40].…”

Insights into the Chemistry, Structure, and Biological Activity of Human Salivary MUC7 Fragments and Their Cu(II) and Zn(II) Complexes

“…Isolated from human salivary secretions, MUC7 exhibits an apparent molecular mass ranging from 150 to 200 kDa, consisting of approximately 30% protein, 68% carbohydrate, and 1.6% sulfate. Recognized as antimicrobial peptides (AMPs), MUC7 and its peptide fragments demonstrate the capacity to bind and inactivate various oral bacteria, including Streptococcus mutans, the periodontal pathogen Actinobacillus actinomycetemcomitans, Pseudomonas aeruginosa, and the yeast Candida albicans . Effective AMPs, derived from the proteolytic hydrolysis of human salivary MUC7, include 20-mer (LAHQKPFIRKSYKCLHKRCR) and 12-mer (RKSYKCLHKRCR) peptide fragments, showcasing antifungal activity and direct bactericidal effects. , Despite the yet unknown exact mechanism underlying MUC7’s antimicrobial actions, current hypotheses suggest the potential involvement of biologically relevant metal ions in this process …”

Rationally Designed Antimicrobial Peptides Are Potential Tools to Combat Devastating Bacteria and Fungi

“…The lipidated analogs did not select resistant mutants in Escherichia coli after repeated exposure to sub-MIC concentrations. In the case of three 15-mer human mucin 7 (MUC7) peptides, a correlation between lipophilicity, the presence of metal ions, and antimicrobial activity against Gram-positive and negative bacteria, as well as fungi, was proven [ 24 ]. Since lipidation has an important role in improving the pharmacokinetic and pharmacodynamic characteristics of natural AMPs, a model lipopeptide was designed and synthesized to examine the effect of the hydrocarbon chain’s length on biological functions and mode of action [ 25 ].…”