The discovery of penicillin over 90 years ago and its subsequent uptake by healthcare systems around the world revolutionised global health and wellbeing. It marked the beginning of a golden age in antibiotic discovery with new classes of antibiotics being routinely discovered and saving millions of lives annually. However, towards the end of the last century, the rate of discovery slowed to a near standstill. This lack of discovery has been compounded by the rapid emergence and spread of bacterial pathogens that exhibit multidrug resistance threatening the sustainability of healthcare systems globally.
Acinetobacter baumannii is a Gram negative coccobacillus that is associated with hospital-acquired infections worldwide. It is an opportunistic pathogen that can colonise a range of anatomical sites in immune-compromised individuals leading to a variety of life-threatening clinical complications. ~2% of all healthcare-associated infections in Europe and USA are caused by this pathogen. The greatest concern associated with this pathogen however is that between 45 - 70% of isolates exhibit multidrug resistance; rates that are significantly higher than those observed for other Gram negative pathogens such as Pseudomonas aeruginosa.
This proposed research project aims to identify compounds that can disrupt the underlying regulatory mechanisms that allow Acinetobacter baumannii to resist treatment and persist in the hospital environment. We will use a combination of custom-designed biosensors, invertebrate model organisms, high throughput screening and artificial models of infection persistence to identify potential new antimicrobials. The mechanism of action of these candidates will then be explored using a range of classical microbiology and genetic approaches. To determine specificity, the impact of these new antimicrobials on the native microbiome will also be investigated using next-generation sequencing technologies.
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