A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis

Toxins (Basel). 2019 Apr 4;11(4):203. doi: 10.3390/toxins11040203.

Abstract

Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 10⁵ cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.

Keywords: LyeTxI-b; Staphylococcus aureus; keratitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / toxicity
  • Antimicrobial Cationic Peptides / chemistry*
  • Arthropod Proteins / administration & dosage*
  • Arthropod Proteins / toxicity
  • Chickens
  • Chorioallantoic Membrane / drug effects
  • Eye / drug effects
  • Eye / immunology
  • Eye / pathology
  • Eye Infections, Bacterial / drug therapy*
  • Female
  • Keratitis / drug therapy*
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Ophthalmic Solutions / administration & dosage*
  • Ophthalmic Solutions / toxicity
  • Rabbits
  • Spider Venoms / administration & dosage*
  • Spider Venoms / toxicity
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Arthropod Proteins
  • LyeTx I protein, Lycosa erythrognatha
  • Ophthalmic Solutions
  • Spider Venoms