Antimicrobial activity and structure of a consensus human β-defensin and its comparison to a novel putative hBD10

Alexis Rodriguez, Marie Pedersen, Elba Villegas, Bruno Rivas-Santiago, Jessica Villegas-Moreno, Carlos Amero, Raymond S. Norton, Gerardo Corzo

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The spread of multidrug resistant bacteria owing to the intensive use of antibiotics is challenging current antibiotic therapies, and making the discovery and evaluation of new antimicrobial agents a high priority. The evaluation of novel peptide sequences of predicted antimicrobial peptides from different sources is valuable approach to identify alternative antibiotic leads. Two strategies were pursued in this study to evaluate novel antimicrobial peptides from the human β-defensin family (hBD). In the first, a 32-residue peptide was designed based on the alignment of all available hBD primary structures, while in the second a putative 35-residue peptide, hBD10, was mined from the gene DEFB110. Both hBDconsensus and hBD10 were chemically synthesized, folded and purified. They showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis, but were not hemolytic on human red blood cells. The NMR-based solution structure of hBDconsensus revealed that it adopts a classical β-defensin fold and disulfide connectivities. Even though the mass spectrum of hBD10 confirmed the formation of three disulfide bonds, it showed limited dispersion in 1H NMR spectra and structural studies were not pursued. The evaluation of different β-defensin structures may identify new antimicrobial agents effective against multidrug-resistant bacterial strains.

Original languageEnglish
Pages (from-to)175-186
Number of pages12
JournalProteins: Structure, Function, and Bioinformatics
Volume88
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • antimicrobial peptides
  • human β-defensins
  • Mycobacterium tuberculosis
  • nuclear magnetic resonance
  • peptide structure
  • peptide synthesis

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