The human gut microbiome as a reservoir of antibiotic resistance

The human gut harbours a complex microbial community (‘the gut microbiome’), which contributes to human health and disease. Previous work by the group of Prof. Van Schaik has revealed that the gut microbiome comprises a large number of antibiotic resistance genes. Current methodologies to study the gut microbiome, like metagenomic shotgun sequencing or high-throughput quantitative PCRs, do not allow for the identification of the bacteria and mobile genetic elements that carry these resistance genes. The extent by which resistance genes can spread between members of the gut microbiome, including to gut-dwelling opportunistic pathogens like Escherichia coli and the enterococci, also remains unclear.

In this project, you will determine to what extent commensal bacteria can serve as reservoirs of antibiotic resistance genes and whether they can transfer these genes to opportunistic pathogens. We will use human stool samples and sewage as sources of resistant bacteria and will employ innovative approaches that rely on single-cell methodologies or cross-linking of resistance genes that are carried on plasmids with bacterial chromosomes, with the aim to identify the bacterial hosts of resistance genes.

Once the identity of the bacteria carrying resistance genes has been established, these strains will be cultured using a variety of enrichment methods. After their isolation, the genomes of the bacteria will be sequenced through a combination of short- and long-read sequencing, resulting in complete assemblies of the chromosome and plasmids. The annotated genome sequences will be used to determine whether resistance genes are associated with mobile genetic elements, specifically plasmids and conjugative elements, or are carried on the chromosome, which would minimize their potential for horizontal transfer. Upon completion of the genomic characterization of the resistance-gene-carrying bacteria, you will perform conjugation assays to assess the ability of these bacteria to serve as donors of resistance genes to the opportunistic pathogens Escherichia coli and Enterococcus faecium.

Ultimately, this project will lead to important new insights into the bacterial reservoirs of antibiotic resistance genes and will importantly deepen our understanding of the mechanisms that contribute to the rapid spread of antibiotic resistance in bacterial ecosystems.


Person Specification
Applicants should have a strong background in microbiology, and ideally with some experience in or affinity with bioinformatics. They should have a commitment to research in the field of antibiotic resistance and the human microbiome and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

To apply please complete the application form at https://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/index.aspx