Examining the complete genome sequences of around two thousand resistant bacteria, mainly Escherichia coli collected between 2008 and 2016, allowed the team to study how different types of resistance genes evolve over time. For example, some genes originated in North America before spreading to Europe, while others were spread to North America from Europe.
Understand the factors that influence the development of antibiotic resistance
The study does not only focus on the geographical origins of bacteria, it also looks at various hosts, such as humans, animals, food (meat) and the environment (sewage). The aim was to understand how these separate but interconnected factors influence the development and spread of antibiotic resistance. Understanding this interconnection exemplifies the One Health approach. It is essential for understanding the dynamics and mechanisms of transmission of resistance genes.
The study was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), a collaboration of 29 countries and the European Commission that aims to stem antibiotic resistance. Without concerted global efforts, antimicrobial resistance will leave millions more vulnerable to infections caused by bacteria and other microorganisms that can currently be treated with antimicrobials.
Study of critical antibiotic resistance genes
The team looked at a particularly important group of antimicrobials, the extended-spectrum cephalosporins. These antibiotics have been classified as “critically important” by the WHO because they are used as a last resort in the treatment of multi-resistant bacteria. Despite this, the effectiveness of these treatments has declined since their appearance due to the resistance developed by the bacteria.
Bacteria develop their resistance to extended-spectrum cephalosporins by producing enzymes called beta-lactamases, which are able to neutralize the action of extended-spectrum cephalosporins.
The manufacture of these enzymes is mainly controlled by two types of genes: those of extended-spectrum beta-lactamases (ESBL) and cephalosporinases (AmpC). These genes can be found on the chromosomes of bacteria when they have been passed on to offspring during cell multiplication, or on plasmids, DNA fragments distinct from chromosomal DNA, which can be transferred directly between bacteria, which represents an alternative means of exchanging genetic material.
This study identifies how certain resistance genes proliferate when multiplying highly successful strains of bacteria, while other genes are transferred directly via plasmids from host to host and between countries.
Understanding the flow of genetic information within bacterial populations and between populations is essential to understand the transmission of antibiotic resistance and its global spread. This understanding will contribute to the development of much-needed actions to curb antimicrobial resistance, in a world where bacteria from diverse hosts and environments interact, and where the international movement of goods and people has broken down the geographical boundaries of these interactions. .
A limited number of strains of bacteria responsible for the spread of resistance to cephalosporins
According to Professor Alison Mather, project leader at the Quadram Institute and the University of East Anglia: “By bringing together such a quantity and diversity of genomes, we have succeeded in identifying the key genes that grant resistance to these treatments. of critical importance. We have also succeeded in proving that resistance to broad-spectrum cephalosporins is in most cases disseminated by a limited number of predominant plasmids and bacterial lineages. Understanding transmission mechanisms is essential for designing actions to limit the spread of antibiotic resistance”.
For lead author, Dr Roxana Zamudio, “Antimicrobial resistance is a global problem, and only collaboration between partners from many countries will allow us to achieve a comprehensive understanding of the geographic spread of antibiotic resistance and its mechanisms. “.