Microbicidal activity of N-chlorotaurine can be enhanced in the presence of lung epithelial cells

J Cyst Fibros. 2020 Nov;19(6):1011-1017. doi: 10.1016/j.jcf.2020.03.005. Epub 2020 Mar 20.

Abstract

Background: N-chlorotaurine (NCT) is an endogenous active chlorine compound that can be used as an antiseptic and anti-infective in different body regions. Recently, tolerability of inhaled NCT has been demonstrated in humans so that it is of interest for future treatment of cystic fibrosis. In the present study, we tested the bactericidal and fungicidal activity of NCT in different lung cell culture models.

Methods: Bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) and fungi (Candida albicans, Exophiala dermatitidis) were co-incubated with lung epithelial cell cultures, and after 4 h NCT was added. After different incubation times, aliquots were removed and quantitative cultures were performed.

Results: NCT at the therapeutically applied concentration of 1% (55 mM) completely killed the test pathogens within 15 - 30 min at 20 °C and at 37 °C. Killing by 0.3% NCT lasted up to 4 h dependent on the pathogen at 20 °C and up to 1 h at 37 °C. 0.1% NCT was the threshold concentration for killing since this amount of oxidation capacity was consumed by reactions with the organic compounds of the medium within 3 h (20 °C) and 0.5 h (37 °C).

Conclusions: NCT in therapeutic concentration demonstrated its microbicidal activity in the presence of lung epithelial cells. Remarkably, particularly the fungicidal activity was higher under these conditions than in phosphate buffer. This can be explained by formation of the stronger microbicidal monochloramine in equilibrium by transchlorination. The results suggest the suitability of NCT as inhalation medication in the lung.

Keywords: Anti-infective; Cystic fibrosis; Lung cells; Microbicidal activity; N-chlorotaurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Cells, Cultured
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / microbiology
  • Epithelial Cells / microbiology*
  • Exophiala / drug effects
  • Lung / cytology*
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Taurine / analogs & derivatives*
  • Taurine / pharmacology

Substances

  • Anti-Infective Agents
  • Antifungal Agents
  • Taurine
  • N-chlorotaurine

Supplementary concepts

  • Exophiala dermatitidis