Research Fellows Directory
Dr Hee-Jeon Hong
University of Cambridge
A decline in the rate of discovery and approval of new antibacterial drugs, coupled with a persistent rise in the numbers and type of drug-resistant bacteria, has highlighted antibiotics as a diminishing resource. Any future development of new drugs with novel antibacterial activities must be underpinned by a detailed understanding of the resistance mechanisms to existing drugs. Because such information is usually linked intimately to the drug’s mode of action this provides unique insights that can help devise novel compounds or new ways of prolonging the therapeutic usefulness of existing ones. Molecular research into antimicrobial resistance mechanisms has generally been narrowly focused on hospital acquired pathogens, but it is now accepted that antibiotic resistance systems originate in the bacterial strains that naturally produce antibiotic compounds, where resistance has co-evolved with the synthesis system. There is however a lack of a detailed understanding of many of the molecular mechanisms that confer antibiotic resistance in producer strains, and of how these are integrated and coordinated with each other. In particular, there is a limited understanding of the mechanisms by which bacterial cells communicate cell envelope damage to their chromosomes, and how the subsequent reprogramming of gene expression acts to counteract the damage. This research proposal addresses these questions, and aims to increase our understanding of the mechanisms by which antibiotic-producing bacteria survive exposure to antibiotics, how they sense different antibiotic drugs, and how they use this information to respond in ways that render the antibiotic harmless to them. A detailed knowledge of how these resistance systems work is fundamental to future approaches in the design of effective, new antibiotics that either cannot be sensed by the bacteria, or that work in novel ways for which resistance mechanisms do not currently exist.
Interests and expertise (Subject groups)