Dr Begoña Heras
Dr Timothy Wells
Menzies Health Institute Queensland Program Seminar Series
Infectious Diseases & Immunology
Infection & Immunity - Host Professor Glen Ulett
Dr Begoña Heras - Title: How autotransporter proteins make bacteria stick
Autotransporters (AT) proteins are the largest group of surface adhesins in Gram-negative bacteria. These proteins play a central role in controlling bacterial interactions with their environment. They allow bacteria to aggregate with other bacteria, adhere to human cells, and form biofilms all key facilitators of bacterial persistence and pathogenesis.
Using a multidisciplinary framework that combines X-ray crystallography, extensive biophysical techniques, immunoassays and cellular assays, we have defined the structure and function of a number of AT proteins. So far, we have found that different AT adhesins promote bacterial aggregation using subtle variations in a conserved "head to tail self-association mechanism". We are also starting to uncover in atomic detail how AT adhesins like UpaB and TibA bind epithelial surfaces. Furthermore, we are beginning to understand how glycosylation regulates the function of multifunctional AT adhesins. We are using this new knowledge to successfully develop methods for disrupting AT function.
Dr Begoña Heras is an ARC Future Fellow at the La Trobe Institute for Molecular Science. She obtained her PhD degree in Organic Chemistry from The University of Navarra (Spain) which led to a postdoctoral position at the John Innes Centre (UK), followed by a senior postdoctoral position at the Institute for Molecular Bioscience (UQ). Since 2012 Dr Heras has been a laboratory head at La Trobe University. Her research focuses on investigating the structure-function relationships in proteins involved in bacterial pathogenesis. Her work has been published in leading international journals including, PNAS, Nature Rev Microbiol, Nature Communications, mBio, and J Biol Chem.
Dr Timothy Wells - Title: The mechanisms and treatment of antibody that exacerbates Pseudomonas aeruginosa lung infections
Chronic Pseudomonas aeruginosa lung infections are found in patients suffering from bronchiectasis and cystic fibrosis (CF) and once colonisation is established, it is difficult to remove by current methods. We previously identified a subset of patients with chronic P. aeruginosa infection that produced specific antibody that protected the infecting bacterium from serum-mediated killing. These "inhibitory antibodies' belong to the IgG2 subclass and target lipopolysaccharide. Crucially, patients with high titres of inhibitory antibodies had worse lung function than patients with normal serum killing. We investigated the mechanisms behind the antibody finding that a high titre alone is not sufficient to predict serum-inhibition, with affinity of the antibodies also important. Additionally, IgA specific for the O-antigen can also inhibit serum mediated killing. Finally, we treated two critically ill patients with inhibitory antibodies with plasmapheresis in an attempt to remove the antibody. Both patients had immediate benefit from this treatment.
Dr Timothy Wells received his PhD from the University of Queensland in 2009 before moving to the University of Birmingham, UK as a Marie Curie Research Fellow. He returned to Australia in 2016, joining the University of Queensland Diamantina Institute to start his own group. His research focuses on the interactions between the host immune system and Pseudomonas aeruginosa during chronic lung infection. Dr Wells is passionate about making his research as clinically relevant as possible, with his work previously having led to novel treatment of critically ill patients. His research uses a mixture of molecular microbiology, immunology and genomic approaches.
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