Effect of antimicrobial peptides HNP-1 and hBD-1 on Staphylococcus aureus strains in vitro and in vivo

Fundam Clin Pharmacol. 2020 Feb;34(1):102-108. doi: 10.1111/fcp.12499. Epub 2019 Aug 5.

Abstract

The aims of this study were: (i) To investigate the activity of recombinant AMPs HNP-1 and hBD-1 in combination with cefotaxime against Staphylococcus aureus strains (MSSA and MRSA) in vitro using checkerboard method; (ii) To investigate the activity of HNP-1 and hBD-1 encapsulated in silicon nanoparticles (niosomes) in the treatment of MRSA-infected wound in rats. For this S. aureus strains (MSSA and MRSA) were isolated from patients with diabetic foot infection. Cefotaxime, recombinant HNP-1 and hBD-1 (in all possible combinations with each other) were used for testing by the checkerboard method. Two niosomal topical gels with HNP-1/hBD-1 were prepared to treat MRSA-infected wounds in rats. Gels were administered once a day, the control group-without treatment. Wound healing rate was calculated on the 4th, 9th and 16th days of the experiment and compared using one-way ANOVA with Bonferroni correction. MIC of HNP-1 for MSSA and MRSA was the same-1 mg/L. MIC of hBD-1 for MSSA and MRSA was also the same-0.5 mg/L. Topical gels with niosomal HNP-1 (or hBD-1) showed a significantly faster wound healing in comparison with the control. The data obtained open up prospects for use of AMPs encapsulated in silica nanoparticles for the development of new antibiotics.

Keywords: Staphylococcus aureus; HNP-1; antibiotic resistance; antimicrobial peptides; hBD-1; silica nanoparticles.

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Cefotaxime / administration & dosage
  • Cefotaxime / pharmacology
  • Diabetic Foot / drug therapy
  • Diabetic Foot / microbiology
  • Drug Therapy, Combination
  • Gels
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Nanoparticles
  • Rats
  • Rats, Wistar
  • Silicon Dioxide / chemistry
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / isolation & purification
  • Wound Healing / drug effects
  • alpha-Defensins / administration & dosage
  • alpha-Defensins / pharmacology*
  • beta-Defensins / administration & dosage
  • beta-Defensins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • DEFB1 protein, human
  • Gels
  • alpha-Defensins
  • beta-Defensins
  • human neutrophil peptide 1
  • Silicon Dioxide
  • Cefotaxime