Novel freeze-substitution electron microscopy provides new aspects of virulent Mycobacterium tuberculosis with visualization of the outer membrane and satisfying biosafety requirements

J Microbiol Methods. 2010 Jan;80(1):14-8. doi: 10.1016/j.mimet.2009.09.022. Epub 2009 Sep 29.

Abstract

Transmission electron microscopy (TEM) of virulent bacteria is usually performed following chemical fixation (CF) with aldehyde fixatives such as glutaraldehyde because of the biosafety problem. However, CF may alter sample ultrastructure. In this study, we used a rapid-freeze substitution (RFS) sandwich method without pre-embedding in agar. TEM images obtained using this method were completely different from those of conventional chemically fixed samples; the bacilli cytoplasm of the RFS preparations was filled evenly with numerous ribosomes, and there was no positional variation of electron density that was obvious in those obtained with CF samples. The sandwich method is suitable for microbiological materials without expensive devices and can be easily performed in a biosafety cabinet. In future, this method coupled with novel labeling techniques may help localize structural and functional molecules throughout a bacterial cell.

Publication types

  • Evaluation Study

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / ultrastructure
  • Fixatives / chemistry
  • Freeze Substitution / methods*
  • Glutaral / chemistry
  • Microscopy, Electron, Transmission / methods*
  • Mycobacterium tuberculosis / chemistry*
  • Mycobacterium tuberculosis / pathogenicity
  • Mycobacterium tuberculosis / ultrastructure
  • Virulence

Substances

  • Bacterial Outer Membrane Proteins
  • Fixatives
  • Glutaral