The rise and spread of antimicrobial resistance is a recognised threat to public health. While much attention has focused on the ‘superbugs’ themselves, the scientific community has largely ignored the plasmids, which act as vehicles for resistance and virulence, and rapidly spread among bacteria. This study investigates plasmids in important human pathogens, Shigella, which causes dysentery, and the gonococcus, a leading cause of sexually transmitted diseases (STD).

Shigella, which kills around 250,000 children worldwide every year, has emerged from ‘friendly bacteria’ after acquiring a single plasmid called pINV.

We will study how pINV is kept by Shigella and how it affects how the bacterium accumulates resistance plasmids. We will use similar approaches to study gonococcal plasmids. Understanding how plasmids are maintained in bacteria should enable us to design strategies to eliminate them, thereby eliminating resistance and virulence from bacteria.

In collaboration with Professor Chris Tang at Oxford University, we aim to decipher phylogenetic diversity and predict transmission pathway(s) of key MDR plasmid groups (so forth virulence plasmids) between commensal (human and animal origins) and enteropathogens (Shigella spp, non-typhoidal Salmonella, ExPEC, K. pneumoniae) identified in the same setting and at similar time frames.

Additionally, we also investigate various exogenous factors (i.e. antibiotics, stress inducers) that may affect the plasmid transfer dynamics and the relevant molecular mechanisms, using transcriptomics and gene function assays.

Using comparative genomic analyses, we will also determine gene candidates that are important for plasmid transfer and stability and manipulate these plasmid genes using CRIPR-cas9 systems. We hope this approach will help to destabilize or remove MDR plasmids from the bacterial hosts at single cell and population levels.