Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infections

FEMS Microbiol Lett. 2016 Aug;363(15):fnw150. doi: 10.1093/femsle/fnw150. Epub 2016 Jun 5.

Abstract

Ten indole alkaloids were obtained from the marine sponge-associated fungus Neosartorya siamensis KUFA 0017. We studied the antimicrobial properties of these and of three other compounds previously isolated from the soil fungus N. siamensis KUFC 6349. Only neofiscalin A showed antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE); with a minimum inhibitory concentration (MIC) of 8 μg mL(-1) against both strains. Another compound, fiscalin C, presented synergistic activity against MRSA when combined with oxacillin, although alone showed no antibacterial effect. Moreover, neofiscalin A, when present at sub-MICs, hampered the ability of both MRSA and VRE strains to form a biofilm. Additionally, the biofilm inhibitory concentration values of neofiscalin A against the MRSA and VRE isolates were 96 and 80 μg mL(-1), respectively. At a concentration of 200 μg mL(-1), neofiscalin A was able to reduce the metabolic activity of the biofilms by ∼50%. One important fact is that our results also showed that neofiscalin A had no cytotoxicity against a human brain capillary endothelial cell line.

Keywords: Neosartorya siamensis; antimicrobial activity; fiscalin C; multidrug-resistant Gram-positive; neofiscalin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Drug Discovery
  • Drug Resistance, Multiple, Bacterial
  • Enterococcus faecalis / drug effects
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / pharmacology*
  • Indole Alkaloids / therapeutic use
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Neosartorya / chemistry
  • Neosartorya / metabolism
  • Oxacillin / pharmacology
  • Quinazolines / pharmacology*
  • Quinazolines / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Indole Alkaloids
  • Indoles
  • Quinazolines
  • fiscalin C
  • Oxacillin