Antipneumococcal activity of neuraminidase inhibiting artocarpin

Int J Med Microbiol. 2015 May;305(3):289-97. doi: 10.1016/j.ijmm.2014.12.004. Epub 2014 Dec 18.


Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia during influenza epidemics. Neuraminidase (NA) is a virulence factor of both pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are structurally related to viral NA and susceptible to oseltamivir, an inhibitor designed to target viral NA. This prompted us to evaluate the antipneumococcal potential of two NA inhibiting natural compounds, the diarylheptanoid katsumadain A and the isoprenylated flavone artocarpin. Chemiluminescence, fluorescence-, and hemagglutination-based enzyme assays were applied to determine the inhibitory efficiency (IC(50) value) of the tested compounds towards pneumococcal NAs. The mechanism of inhibition was studied via enzyme kinetics with recombinant NanA NA. Unlike oseltamivir, which competes with the natural substrate of NA, artocarpin exhibits a mixed-type inhibition with a Ki value of 9.70 μM. Remarkably, artocarpin was the only NA inhibitor (NAI) for which an inhibitory effect on pneumococcal growth (MIC: 0.99-5.75 μM) and biofilm formation (MBIC: 1.15-2.97 μM) was observable. In addition, we discovered that the bactericidal effect of artocarpin can reduce the viability of pneumococci by a factor of >1000, without obvious harm to lung epithelial cells. This renders artocarpin a promising natural product for further investigations.

Keywords: Antipneumococcal; Artocarpin; Biofilm; DANA; Katsumadain A; NanA; Neuraminidase; Neuraminidase inhibitors; Oseltamivir; Pneumococci; Zanamivir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Diarylheptanoids / pharmacology
  • Enzyme Inhibitors / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Mannose-Binding Lectins / pharmacology*
  • Mannose-Binding Lectins / toxicity
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Plant Lectins / pharmacology*
  • Plant Lectins / toxicity
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / physiology


  • Anti-Bacterial Agents
  • Diarylheptanoids
  • Enzyme Inhibitors
  • Mannose-Binding Lectins
  • Plant Lectins
  • artocarpin lectin
  • katsumadain A
  • Neuraminidase