ResCap - A new metagenomic weapon against antimicrobial resistance

Will next generation sequencing provide a breakthrough in the constantly evolving struggle against antibiotic resistance?

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Feb 01, 2017
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Article highlights

  • First Target sequence capture for the resistome
  • Very sensitive and specific compared to other methods
  • Can identify resistance genes in complex populations

The microbiomes of at-risk hospital patients can often be a source of antibiotic resistance genes that are either selected for or transferred to pathogens when undergoing antibiotic treatment.

Knowing the resistance genes present in any given patient can help medical staff prescribe the right antibiotics, or at least have an idea of which ones to avoid. As sequencing technologies become more available in the hospital, there is a real chance they could be used looking for resistance genes in individual patients.

There's a problem though.

According to Lanza et al. the resistance genes make up only 0.2% of all the genes from the human gut metagenome. This means that if you collect a sample from a patient, only 0.2% of the DNA that you get is going to contain the resistance genes that you are interested in.

So how on earth do you detect them?

This is where ResCap by Lanza et al. comes in. The use a target sequence capture platform to enrich resistome genes before sequencing and using new bioinformatic tools to analyse them. As described in the abstract below, they incorporate over 8 thousand resistance genes and nearly 80 thousand homologues. Despite this, their test show that ResCap is much more sensitive than comparable methods such as metagenomic shotgun sequencing.


Read the abstract below. Link and reference at the bottom of the article.

In-Depth Resistome Analysis by Targeted Metagenomics

Abstract

We developed ResCap, a targeted sequence capture platform based on SeqCapEZ technology, to analyse resistomes and other genes related to antimicrobial resistance (heavy metals, biocides and plasmids). ResCap includes probes for 8,667 canonical resistance genes (7,963 antibiotic resistance genes and 704 genes conferring resistance to metals or biocides), plus 2,517 relaxase genes (plasmid markers). Besides, it includes 78.600 genes homologous to the previous ones (47,806 for antibiotics and 30,794 for biocide or metals). ResCap enriched 279-fold the targeted sequences detected by metagenomic shotgun sequencing and improves their identification. Novel bioinformatic approaches allow quantifying 'gene abundance' and 'gene diversity'. ResCap, the first targeted sequence capture specifically developed to analyse resistomes, enhances the sensitivity and specificity of available metagenomic methods to analyse antibiotic resistance in complex populations, enables the analysis of other genes related to antimicrobial resistance and opens the possibility to accurately study other complex microbial systems.

Reference

Val F Lanza, Fernando Baquero, Jose Luis Martinez, Ricardo Ramos-Ruiz, BrunoGonzalez-Zorn, Antoine Andremont, Antonio Sanchez-Valenzuela, Dusko Ehrlich, SeanKennedy, Etienne Ruppe, Willem van Schaik, Rob J Willems, Fernando de la Cruz, Teresa M Coque

Go to the profile of Ben Libberton

Ben Libberton

Communications Officer, MAX IV Laboratory

I'm a Communications Officer at MAX IV Laboratory in Lund, Sweden, formally a Postdoc in the biofilm field. I'm interested in how bacteria cause disease and look to technology to produce novel tools to study and ultimately prevent infection. Part of my current role is to find ways to use synchrotron radiation to study microorganisms.

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