Tracking the global spread of antimicrobial resistance

Escherichia coli. Credit: Rocky Mountain Laboratories, NIAID, NIH

An international research team has provided valuable new insight into what drives the global spread of genes responsible for antimicrobial resistance (AMR) in bacteria.

The collaborative study, led by researchers from the Quadram Institute and the University of East Anglia, brought together experts from France, Canada, Germany and the UK and will provide new information to combat the global challenge of antimicrobial resistance.

By examining the whole genome sequences of around 2,000 resistant bacteria, predominantly Escherichia coli collected between 2008 and 2016, the team found that the different types of AMR genes varied in their temporal dynamics. For example, some were initially found in North America and spread to Europe, while others spread from Europe to North America.

The study not only looked at bacteria from different geographic regions, but also from various hosts, including humans, animals, food (meat), and the environment (wastewater), to define how these separate but interconnected factors influenced development and survival. AMR propagation. Understanding this interconnectedness embodies the One Health approach and is vital to understanding the transmission dynamics and mechanisms by which resistance genes are passed on.

The study, published in the journal nature communications, was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), a global collaboration spanning 29 countries and the European Commission tasked with turning the tide on AMR. Without concerted efforts on a global scale, AMR will undoubtedly make millions more people vulnerable to infections by bacteria and other microorganisms that can currently be combated with antimicrobials.

The team focused on resistance to a particularly important group of antimicrobials, the extended-spectrum cephalosporins (ESCs). These antimicrobials have been classified as critically important by the World Health Organization because they are a “last resort” treatment for multidrug-resistant bacteria; despite this, since its introduction, efficacy has declined as bacteria have developed resistance.

Bacteria that are resistant to ESCs do this by producing specific enzymes, called beta-lactamases, that can inactivate ESCs.

The instructions for making these enzymes are encoded in genes, particularly in two key types of genes: extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases (AmpCs).

These genes can be found on the chromosomes of bacteria where they are passed on to progeny during clonal multiplication, or on plasmids, which are small DNA molecules separate from the main chromosome of the bacterium. Plasmids are mobile and can move directly between individual bacteria, representing an alternative way of exchanging genetic material.

This study identified how some resistance genes proliferated through clonal expansion of particularly successful bacterial subtypes, while others were directly transferred on epidemic plasmids across different hosts and countries.

Understanding the flow of genetic information within and between bacterial populations is key to understanding the transmission of AMR and the global spread of resistance. This knowledge will contribute to the design of vitally needed interventions that can stop AMR in the real world where bacteria from diverse hosts and environmental niches interact, and where international travel and trade mean these interactions are not limited by geography.

Professor Alison Mather, Group Leader at the Quadram Institute and the University of East Anglia, said: “By assembling such a large and diverse collection of genomes, we were able to identify the key genes that confer resistance to these critically important drugs. We were also able to able to demonstrate that most extended-spectrum cephalosporin resistance is spread only by a limited number of predominant plasmids and bacterial lineages; understanding the mechanisms of transmission is key to designing interventions to reduce the spread of AMR.”

Lead author Dr Roxana Zamudio said: “Antimicrobial resistance is a global problem, and only by working collaboratively with partners in multiple countries can we gain a holistic understanding of where and how AMR is spreading.”

More information:
Dynamics of extended-spectrum cephalosporin resistance genes in Escherichia coli from Europe and North America. nature communications (2022). DOI: 10.1038/s41467-022-34970-7

Provided by the University of East Anglia

Citation: Tracking the Global Spread of Antimicrobial Resistance (2022, December 12) Accessed December 12, 2022 at

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