Elucidating the gene exchange networks of antibiotic resistance genes in clinical sewage microbiomes
Antibiotics are essential for treating bacterial infections. However, antimicrobial resistance (AMR) has spread among pathogenic bacteria, leading to therapy failure or deaths of patients. Due to their association with promiscuous mobile genetic elements, clinically important antibiotic resistance genes (ARGs) can spread rapidly among diverse bacteria through horizontal gene transfer (HGT). Due to HGT, identifying the microbial hosts of the ARGs in an ecosystem is a challenge. Importantly, it has been shown that ARGS can spread from human gut commensals to clinical pathogens and vice versa. 

Wastewater from clinical sources can importantly select for HGT of ARGs between different microbes, as both antibiotics and ARGs are present at high levels. The aim of this project - ""ARCS"" (Antibiotic Resistance in Clinical Sewage microbiomes), is to reveal the ARGs exchange networks in clinical sewage microbiomes. The research objectives are: 1) Link ARGs to microbial hosts by using novel culture-independent methods based on DNA high-throughput sequencing. 2) Link ARGs to mobile genetic elements by isolating, sequencing, and characterizing the genomes of the identified hosts of ARGs. 3) Evaluate whether the isolates can transfer their ARGs to clinical pathogens using conjugation assays. ARGS will thus lead to a step-change in our understanding of HGT of ARGs in complex microbial ecosystems. 

The Fellow Dr. Lisandra Zepeda's expertise in generating and analysing DNA sequencing data and the host Prof. Willem van Schaik's international leadership in AMR ensure a successful completion of ARCS and a favourable knowledge transfer for both parties. Furthermore, the supportive environment of the University of Birmingham ensures the accomplishment of the Fellow's training in crucial areas such as microbial DNA capture sequencing, microbiology laboratory techniques, and mentoring skills. Thus, ARCS will enable Dr. Zepeda to realise her career goal of becoming a research group leader.