Article: HL-SAN used in metagenomic diagnosis to battle multi-resistant bacteria

In a paper published in Nature Biotechnology, Justin O’Grady’s group at the Quadram Institute in Norwich (UK), a leading entity on molecular diagnostics of pathogens, has used HL-SAN from ArcticZymes as a critical component in a novel and rapid method for diagnosing bacterial lower respiratory infections (LRIs).

The current gold standard for diagnosing bacterial LRIs typically requires 48 – 72 hours to identify the pathogen. Waiting 2 – 3 days before initiating targeted antibiotic treatment is not an option when facing severe infections, and the decision is usually made to initiate treatment with broad-spectrum antibiotics immediately. This practice comes with the risk of evolving new antibiotic resistant bacteria. To avoid over-use of antibiotics and allow targeted treatment, new technologies are needed which within hours can identify the infection-causing pathogen. This is particularly relevant for respiratory tract infections, as they account for 60% of the antibiotics prescribed in general practice in the UK.

Metagenomics is a method where all the DNA in a specific sample is sequenced. This allows not only detection of rare and unexpected pathogens but can also offer information about any antibiotic resistances of the pathogens. Metagenomic sequencing of human samples can be difficult due to the vast amount of DNA originating from the patient compared to the very small amounts of pathogen DNA in the sample. To avoid this problem, the patient DNA must be removed prior to bacterial cell lysis and sequencing.

In their article, Charalampous et al. describe how using a detergent at very high salt concentrations makes human DNA more accessible for nuclease-digestion while keeping the pathogens in the sample intact. However, using nucleases to remove unwanted DNA at very high salt concentrations is generally not effective due to their low tolerance to salt. HL-SAN from ArcticZymes, a nuclease originating from the saline marine environments in the Arctic, actually prefers high salt conditions and thereby provides a perfect match for this approach.

By using HL-SAN as a key component in their work, the researchers were able to use metagenomics to identify LRI-causing pathogens as well as accurately detect resistance against antibiotics within a time span of 6 hours. This allows targeted treatment to begin within a working day.

ArcticZymes is proud to learn that one of our products can be used to reduce the threat multi-resistant bacteria is posing to the public. We also acknowledge that metagenomics holds great promise for diagnosis and analysis on a large variety of sample material. It is envisioned that HL-SAN can be an important component in technologies targeting the growing metagenomic diagnosis market.

Reference: Charalampous, T., et al. (2019). “Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection.” Nature Biotechnology 37(7): 783-792.

A preprint of the paper is available here.