Extraction of high-molecular-weight DNA from Streptococcus spp. for nanopore sequencing in resource-limited settings

Microbiologyopen. 2024 Aug;13(4):e1432. doi: 10.1002/mbo3.1432.

Abstract

The long-read sequencing platform MinION, developed by Oxford Nanopore Technologies, enables the sequencing of bacterial genomes in resource-limited settings, such as field conditions or low- and middle-income countries. For this purpose, protocols for extracting high-molecular-weight DNA using nonhazardous, inexpensive reagents and equipment are needed, and some methods have been developed for gram-negative bacteria. However, we found that without modification, these protocols are unsuitable for gram-positive Streptococcus spp., a major threat to fish farming and food security in low- and middle-income countries. Multiple approaches were evaluated, and the most effective was an extraction method using lysozyme, sodium dodecyl sulfate, and proteinase K for lysis of bacterial cells and magnetic beads for DNA recovery. We optimized the method to consistently achieve sufficient yields of pure high-molecular-weight DNA with minimal reagents and time and developed a version of the protocol which can be performed without a centrifuge or electrical power. The suitability of the method was verified by MinION sequencing and assembly of 12 genomes of epidemiologically diverse fish-pathogenic Streptococcus iniae and Streptococcus agalactiae isolates. The combination of effective high-molecular-weight DNA extraction and MinION sequencing enabled the discovery of a naturally occurring 15 kb low-copy number mobilizable plasmid in S. iniae, which we name pSI1. We expect that our resource-limited settings-adapted protocol for high-molecular-weight DNA extraction could be implemented successfully for similarly recalcitrant-to-lysis gram-positive bacteria, and it represents a method of choice for MinION-based disease diagnostics in low- and middle-income countries.

Keywords: MinION rapid sequencing; Streptococcus; Streptococcus iniae plasmid; high‐molecular‐weight DNA extraction; nanopore; resource‐limited settings.

MeSH terms

  • Animals
  • DNA, Bacterial* / genetics
  • Fish Diseases / microbiology
  • Fishes / microbiology
  • Genome, Bacterial / genetics
  • Molecular Weight
  • Nanopore Sequencing* / methods
  • Resource-Limited Settings
  • Sequence Analysis, DNA / methods
  • Streptococcal Infections / microbiology
  • Streptococcus* / classification
  • Streptococcus* / genetics
  • Streptococcus* / isolation & purification

Substances

  • DNA, Bacterial