Antibiotic resistance (AbR) is a global health threat. Bacteria like Escherichia coli and Klebsiella pneumoniae share antibiotic resistance genes via plasmids, which are self-replicating genetic entities that move freely between bacterial cells (by conjugation). Importantly, once acquired, these plasmids become fixed in the bacterial accessory genome because they encode specific ‘addiction systems’ that poison any cells from which the AbR plasmid is lost. Cross-interference between plasmid replication systems ensures that related plasmids do not co-exist within the same bacterial cell. This incompatibility (Inc) means that if a plasmid is strongly selected for (e.g. by an antibiotic), any bacterium that acquires it will lose any incompatible plasmid and no related plasmid can enter thereafter.
Our ultimate goal is to eradicate antibiotic resistance from dangerous multi-resistant enteric bacteria by replacing the plasmids that carry this resistance with ‘healthy’ (sensitive) plasmids, without killing the bacterial host, re-establishing a healthy (antibiotic-susceptible) microflora.
Aims of our project are:
- define the replication and addiction systems in the most important naturally-occurring AbR plasmids causing concern around the world
- testing effects of key host range determinants (entry/exclusion systems, incompatibility and addiction systems, and conjugation/mobilisation) and
- develop therapeutic plasmids to eradicate the most important AbR plasmids in the Enterobacteriaceae.
Project supervisor: Muhammed Kamruzzaman | firstname.lastname@example.org