INTERNATIONAL GRANT 2022

ANNUAL THEME

"Structure and function of the gut microbiota resistome" 

The proposal will explore the functional role of antibiotic resistance genes within the gut microbiome, with a focus on anaerobic microorganisms that are difficult to assess in routine clinical microbiology

SUPPORTED PROJECT

Søren Johannes Sørensen Professor, Ph.D.

Søren Johannes Sørensen Professor, Ph.D.
Section of Microbiology
Department of Biology
University of Copenhagen

Linking the early life resistome and microbiome maturation

PROJECT DESCRIPTION

The first years of life are pivotal for establishing a mature gut microbiome and proper development of the host immune system. The antibiotic resistome is introduced in the infant gut along with the developing gut microbiome in early life.

We recently showed that antibiotic resistance gene (ARG) enrichment in early life was associated with gut microbial immaturity, similar to asthma-associated microbiome composition. However, the potential drivers for ARG acquisition in early life, the maintenance of ARGs, and how the early life resistome interferes with gut microbial maturation and immune development are unclear.

ARGs can be exchanged among diverse species through horizontal gene transfer (HGT) via plasmids, which significantly facilitates the evolution of multi-drug resistance and the emergence of novel “superbugs” in pathogens. Co-selection between ARGs and other resistance genes can confer a selective advantage for ARGs in bacterial hosts and further promote their persistence of bacterial hosts.

In this project, we will focus on “HGT” and “co-selection” to expand our understanding on ARG dynamics, and its potential effect on gut microbial maturation. Approximately 80% of human gut bacterial species detected by molecular tools are unculturable, especially the specialized anaerobes inhabiting the gut. Hence, this project, will reconstruct known and unknown genomes and plasmids directly from metagenomic sequencing data on longitudinal samples consisting of approximately 700 infants from COPSAC 2010 cohort at each time point (1 week, 1 month, 1 year, 10 year), to address our hypothesis.

This project consists of three aspects:

  • Analyze the longitudinal colonization pattern of the early gut resistome.
  • Analysis of HGT in the early gut microbiome via plasmids.
  • Co-localization analysis between ARGs and other resistance genes.

This ambitious proposal will facilitate a breakthrough in our understanding of the evolution and dissemination of antimicrobial resistance in the early life human gut.