Director's Seminar Series - Associate Professor Amy Cain, Macquarie University

Molecular mechanisms underpinning co-infection and stress response in hospital pathogens

 

Host: Professor Si Ming Man

 

Abstract

In the modern age of ‘omics technologies, our increased understanding of antibiotic resistance, microbial pathogenicity and host-pathogen interactions hinges on applying innovative molecular studies to bacterial pathogens. In this work, we develop functional genomics techniques, like transposon insertion sequencing (TIS) and transcriptomics, and use comparative genomics to examine infection-relevant stresses in various hospital-associated pathogens through multiple molecular lenses.

My research 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 mixed bacterial populations. We elucidate how bacterial pathogens work together to co-infect efficiently, cross-feed each other and promote cross-resistance. We utilise the Galleria mellonella insect model to evaluate the toxicity and efficacy of novel antimicrobials and to evaluate virulence gene function. 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.

This work demonstrates the varied capabilities of functional genomics in understanding bacterial resistance and stress tolerance, as well as co-infection strategies and showcases the Galleria model as an important step towards effective antibiotic development and in understanding pathogen infection.

 

Biography

A/Prof Amy Cain gained her PhD in Microbiology from the University of Sydney, investigating movement of antibiotic resistance genes in Salmonella between animals and humans. Next Amy moved to Cambridge (UK) to work at the Wellcome Sanger Institute developing bespoke genomics techniques to examine antibiotic resistance gene networks. Then she moved to Malawi, tracking and sequencing hospital-acquired resistant infections as part of the Malawi-Liverpool-Wellcome Clinical Research Program. Next, she joined the Vertex Pharmaceuticals, working between Oxford (UK) and Boston (USA) to develop new antibiotics. In 2018, Amy moved back to Australia to establish her own group at Macquarie University as an ARC DECRA Fellow.

Currently Amy is an ARC Future Fellow, situated across the School of Natural Sciences, the ARC Centre of Excellence in Synthetic Biology and Applied Biosciences and focuses on developing new antibiotics and understanding bacterial stress response using functional genomics techniques, novel single-cell microfluidics-based methodology and adaptive evolutionary approaches. She also builds synthetic microbes that efficiently degrade various waste materials, like plastics. She established and is director the Galleria Research Facility, Australia’s first high-throughput in vivo model which is used to assess the pathogenicity of microbes, and the toxicity and efficacy of new drugs.