Generating whole bacterial genome sequences of low-abundance species from complex samples with IMS-MDA

Nat Protoc. 2013 Dec;8(12):2404-12. doi: 10.1038/nprot.2013.147. Epub 2013 Nov 7.

Abstract

The study of bacterial populations using whole-genome sequencing is of considerable scientific and clinical interest. However, obtaining bacterial genomic information is not always trivial: the target bacteria may be difficult to culture or uncultured, and they may be found within samples containing complex mixtures of other contaminating microbes and/or host cells, from which it is very difficult to derive robust sequencing data. Here we describe our procedure to generate sufficient DNA for whole-genome sequencing from clinical samples and without the need for culture, as successfully used on the difficult-to-culture, obligate intracellular pathogen Chlamydia trachomatis. Our protocol combines immunomagnetic separation (IMS) for targeted bacterial enrichment with multiple displacement amplification (MDA) for whole-genome amplification (WGA), which is followed by high-throughput sequencing. Compared with other techniques that might be used to generate such data, IMS-MDA is an inexpensive, low-technology and highly transferable process that provides amplified genomic DNA for sequencing from target bacteria in under 5 h, with little hands-on time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Chlamydia trachomatis / genetics
  • DNA, Bacterial / chemistry*
  • Genome, Bacterial*
  • Genomics
  • Immunomagnetic Separation / methods*
  • Nucleic Acid Amplification Techniques / methods
  • Sequence Analysis, DNA / methods

Substances

  • DNA, Bacterial