Targeting Intrinsic Mechanisms of Antibiotic Resistance in Bacterial Pathogens

The prevalence of bacterial antibiotic resistance continues to rise; there is a need for new safe and effective antibiotics. This is a recognised need in both public health and biodefence. Drug development is a lengthy, complex, and costly process, entrenched with a high degree of uncertainty that a drug will succeed. Consequently, the investment into drug development by Pharma is in decline. Research using high throughput genomics based approaches continues to identify novel bacterial targets with the aim of stimulating drug discovery efforts for those targets externally. These studies have recently identified the genes that are required by bacteria to resist antibiotics. Therefore, this project will utilise this new data to investigate a novel antibacterial approach that aims to disable the intrinsic bacterial resistance mechanisms thereby allowing antibiotic therapies to effectively treat and clear infections. If successful, this approach could have broad utility for treatment of both intrinsically-resistant pathogens (e.g Yersinia, Citrobacter, Proteus, Burkholderia) and those which acquire similar resistance mechanisms on exposure to the drugs (e.g. Klebsiella sp., E. coli). This is likely to lead to pre-clinical therapeutic candidates which will be evaluated in microbiological assays and models.