Track-AMR: Track antimicrobial resistance genes by metagenomics in enteric pathogens

Drivers of antimicrobial resistance in enteric pathogens: proximity-ligation metagenomics to track antimicrobial resistance genes across microbes in space and time. (Track-AMR)

In Track-AMR, the Amsterdam University Medical Center partners with Phase Genomics (Seattle, USA) to employ a technology called proximity-ligation sequencing (Hi-C) to understand how bacteria that cause diarrhea in children in low-and middle-income settings can become resistant to antibiotics. 

Diarrhea is the second major killer of children in LMIC-settings and they are extra vulnerable to developing bacterial infections that are resistant to antibiotic treatment. The rapidly rising numbers of infections with antimicrobials resistant bacteria represents a major threat to global health, killing more than 1.27 million people per year.

We aim to fill an important knowledge gap in AMR research, namely: how do bacterial enteropathogens acquire genes that encode antimicrobial resistance and what are the roles of antibiotic usage and the bacteria in our gut (the human microbiome) in this process. The human microbiome is known to carry numbers of antimicrobial resistance genes, but current technologies have not let us sufficiently understand how they spread among different bacteria.

The development of proximity-ligation sequencing technology (Hi-C) by Phage Genomics allows scientists to tracking the spread of antimicrobial resistance between bacteria that live in our gut and bacteria that can cause disease.. In this project we will study the spreadof these genes over time in fecal samples from children from Zambia and Ghana who have developed an episode of bacterial diarrheal disease.   

The generated datasets will be used to characterise and quantify the spread of antibiotic resistance genes following antibiotics and during diarrheal infections. We will develop methodologies to pinpoint how the genes are transferred (horizontal transfer events). This work will uncover the developing human microbiome’s role as a reservoir for antibiotic resistance. These insights are needed to design evidence-based interventions to stop the spread of antibiotic resistance genes within our microbiome and towards bacteria that are capable of causing diarrheal disease.

Summary
In this project, we aim to fill an important knowledge gap in antimicrobial resistance research, namely: how do bacterial enteropathogens acquire antimicrobial resistance genes and what are the roles of antibiotic usage and the indigenous human microbiome in this process.
Technology Readiness Level (TRL)
1 - 3
Time period
24 months
Partners