Novel antibiotic resistance genes discovered

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Research from Chalmers University of Technology and the University of Gothenburg (both Gothenburg, Sweden) have discovered several previously unknown genes involved in bacterial resistance to the last-resort antibiotics carbapenems.

The study, published recently in Microbiome, predicted 76 novel B1 metallo-β-lactamases by analyzing large volumes of bacterial DNA. These bacterial enzymes provide resistance to carbapenems, one of our most powerful classes of antibiotics, and are commonly encoded on mobile genetic elements, a feature that makes them a particularly problematic class of antibiotic resistance determinants.

Principal investigator, Erik Kristiansson (Chalmers University of Technology), commented: “Our study shows that there are lots of unknown resistance genes. Knowledge about these genes makes it possible to more effectively find and hopefully tackle new forms of multi-resistant bacteria.”

Co-author, Joakim Larsson (University of Gothenburg) explained: “The more we know about how bacteria can defend themselves against antibiotics, the better are our odds for developing effective, new drugs.”

Identifying resistance genes can be challenging, particularly if they haven’t been encountered before. To overcome this, the team utilized an optimized hidden Markov model to develop a computational method that allowed them to discover patterns in bacterial genomes associated with antibiotic resistance.

The researchers analyzed more than 10,000 bacterial genomes and plasmids along with over 5 terabases of metagenomic data, predicting 76 novel genes conferring carbapenem resistance.To confirm if these predictions were correct the team experimentally confirmed the ability to hydrolyze imipenem in an Escherichia coli host, demonstrating this in 18 of the 21 tested genes.

This study over doubles the number of currently identified B1 metallo-β-lactamases, elucidating the diversity and evolutionary history of this important class of resistance genes. The team hopes this knowledge could help us prepare for some of the clinical challenges we may face in the future. Looking forwards, the researchers are aiming to investigate genes that provide resistance to other forms of antibiotics.

Kristiansson concluded: “The novel genes we discovered are only the tip of the iceberg. There are still many unidentified antibiotic resistance genes that could become major global health problems in the future.”

Sources: Berglund F, Marathe NP, Österlund T et al. Identification of 76 novel B1 metallo-β-lactamases through large-scale screening of genomic and metagenomic data. Microbiome. 5(134) doi:10.1186/s40168-017-0353-8 (2017); www.eurekalert.org/pub_releases/2017-10/cuot-nar101317.php

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