Antibiofilm activities of norharmane and its derivatives against Escherichia coli O157:H7 and other bacteria

Phytomedicine. 2017 Dec 1:36:254-261. doi: 10.1016/j.phymed.2017.10.013. Epub 2017 Oct 20.

Abstract

Background: Bacterial biofilms exhibit reduced sensitivity to conventional antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections.

Hypothesis: The antibiofilm approach using plant alkaloids provides an alternative to antibiotic strategies.

Study design: In this study, the antibiofilm activities of various plant alkaloids were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa. In the subsequent investigation, the effects of five norharmane derivatives were investigated.

Result: Harmaline significantly inhibited biofilm formation by E. coli O157:H7, P. aeruginosa PAO1, P. aeruginosa PA14, and Klebsiella oxytoca, and norharmane (β-carboline) was found to have antibiofilm activity. It was also found that functional groups at the C-1 and C-7 positions of norharmane could play important roles in its antibiofilm activity. Confocal and electron microscopic observations confirmed biofilm inhibition by harmaline and norharmane, and both reduced fimbriae production and swarming and swimming motilities. Furthermore, harmaline and norharmane attenuated the virulence of E. coli O157:H7 in a Caenorhabditis elegans nematode model.

Conclusion: These findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections.

Keywords: Antivirulence; Biofilm; Escherichia coli O157:H7; Harmaline; Norharmane; Pseudomonas aeruginosa.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Caenorhabditis elegans / microbiology
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Escherichia coli Infections / drug therapy
  • Escherichia coli O157 / drug effects*
  • Escherichia coli O157 / pathogenicity
  • Escherichia coli O157 / physiology
  • Klebsiella oxytoca / drug effects
  • Klebsiella oxytoca / physiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / physiology

Substances

  • Anti-Bacterial Agents
  • Carbolines
  • norharman