Direct mass spectrometric screening of antibiotics from bacterial surfaces using liquid extraction surface analysis

Rapid Commun Mass Spectrom. 2012 Oct 30;26(20):2477-82. doi: 10.1002/rcm.6365.

Abstract

Rationale: There is a need to find new antibiotic agents to fight resistant pathogenic bacteria. To search successfully for novel antibiotics from bacteria cultivated under diverse conditions, we need a fast and cost-effective screening method.

Methods: A combination of Liquid Extraction Surface Analysis (LESA), automated chip-based nanoelectrospray ionization, and high-resolution mass or tandem mass spectrometry using an Orbitrap XL was tested as the screening platform. Actinobacteria, known to produce well-recognized thiazolyl peptide antibiotics, were cultivated on a plate of solid medium and the antibiotics were extracted by organic solvent mixtures from the surface of colonies grown on the plate and analyzed using mass spectrometry (MS).

Results: LESA combined with high-resolution MS is a powerful tool with which to extract and detect thiazolyl peptide antibiotics from different Actinobacteria. Known antibiotics were correctly detected with high mass accuracy (<4 ppm) and structurally characterized using tandem mass spectra. Our method is the first step toward the development of a novel high-throughput extraction and identification tool for antibiotics in particular and natural products in general.

Conclusions: The method described in this paper is suitable for (1) screening the natural products produced by bacterial colonies on cultivation plates within the first 2 min following extraction and (2) detecting antibiotics at high mass accuracy; the cost is around 2 Euro per sample.

MeSH terms

  • Actinobacteria / cytology
  • Actinobacteria / metabolism*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / metabolism
  • Bacterial Adhesion
  • Humans
  • Liquid-Liquid Extraction / methods*
  • Peptides / chemistry
  • Peptides / isolation & purification*
  • Peptides / metabolism
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Thiazoles / chemistry
  • Thiazoles / isolation & purification*
  • Thiazoles / metabolism

Substances

  • Anti-Bacterial Agents
  • Peptides
  • Thiazoles