The human gut microbiome is a community of microorganisms, including many species of bacteria, viruses and fungi that play a vital role in human health. These bacteria, particularly those within the gastrointestinal tract, have been linked to several diseases including inflammatory bowel disease and metabolic disease. However, what we now know is that these bacteria harbor antimicrobial resistance (AMR) genes that can be transferred between bacterial species, including pathogens. Currently, studies looking at this transfer of resistance have only been able to use sequencing data to infer that a transfer event has occurred, and they have not been able to culture many of the bacterial species involved. These studies have also relied upon the previous annotations of AMR genes and so have not been able to identify any novel modes of resistance.
This project is assessing the mechanism and frequency of AMR transfer from the commensals in the gut microbiota to gut enteropathogens. Initially, commensals from the gut microbiome were screened for resistance to three antibiotics (Tetracycline, Amoxicillin-clavulanic acid, and Vancomycin), and resistant strains were collected to form a panel of 95 AMR strains. This panel of AMR commensals was then mixed with either Enterococcus feacium or Klebsiella pneumoniae. The transfer of resistance has been phenotypically determined and the genes which have been transferred have been identified through whole genome sequencing of transconjugants. This work has identified AMR genes and mobile genetic elements capable of transfer between gut commensal bacteria and enteropathogens. Analysis has demonstrated shared phenotypic activity and phylogenetic barriers for transfer. These results will allow for more tailored treatments for patients with bacterial infections to improve treatment outcomes and reduce spread of AMR, and aid potential development of novel antimicrobials.