In the modern age of ‘omics technologies, our increased understanding of antibiotic resistance, microbial pathogenicity and host-pathogen interactions hinges on developing innovative molecular studies on bacterial pathogens. In this work, we develop functional genomics techniques, like transposon insertion sequencing (TIS) and transcriptomics, and use comparative genomics to examine antibiotic resistance in various hospital pathogens through multiple molecular lenses.
Our group characterises complex resistance mechanisms that bacterial pathogens use to evade antibiotic treatment and evaluates the evolution of antibiotic resistance and stress tolerance over time. We use larger scale genomics to track antibiotic resistance spread across hospitals and single cell genomics for fine resolution within populations, such as heteroresistance and intraspecies competition. We utilise the Galleria mellonella insect model to evaluate the toxicity and efficacy of novel antimicrobials and use TIS to outline antibiotic mechanisms of action. We also assay the function of bacterial pathogenesis genes; for example, assessing the function of a stress-protection regulator DksA from the pathogen Acinetobacter baumannii.
Our work demonstrates the varied capabilities of functional genomics in understanding bacterial resistance and stress tolerance and showcases the Galleria model as an important step towards effective antibiotic development and in understanding pathogen infection.