The orchestration of life and death by bacterial gut pathogens
Bacterial gut pathogens specifically target and inactivate multiple innate immune signaling mechanisms in order to remain undetected by the host, persist and cause disease. Pathogenic E. coli, Salmonella, and Shigella all utilise a needle-like injection apparatus called a type III secretion system (T3SS) to inject virulence proteins (effectors) directly into the cytosol of infected host cells. A subset of these injected effectors specifically target pro-survival or programmed cell death pathways for post-translational modification or proteasomal degradation. This allows the bacteria to effectively ‘hide’ from host immune alert mechanisms, by, for example, inhibiting inflammatory cytokine production as well as apoptosis, necroptosis and pyroptosis. Our work has revealed a number of novel mechanisms of bacterial effectors in vitro, and in vivo. Specifically, we have recently identified RIPK1 (receptor interacting serine/threonine protein kinase-1) as a critical innate immune factor for controlling bacterial gut infection. Recent identification of humans with biallelic RIPK1 mutations show patients suffered severe, recurrent mucosal infections, intestinal inflammation, and a 40% mortality rate. Therefore, we are currently investigating the underlying mechanisms of severe intestinal disease mediated by RIPK1 loss using our in vivo models of bacterial gut infection.
Jaclyn completed her PhD in the Department of Microbiology and Immunology at the University of Melbourne in 2013, studying the complex interactions between host and microbe. In 2014, Jaclyn was awarded an NHMRC Peter Doherty ECF and in 2019, received further funding as an NHMRC Career Development Fellow. Jaclyn has been the recipient of numerous awards including the 2017 L’Oréal for Women in Science Fellowship and the Victorian Premier’s Award for Health and Medical Research in 2014. In 2017, Jaclyn was recruited to the Hudson Institute as leader of the Host-Pathogen Interactions Group in the Centre for Innate Immunity and Infectious Diseases.
The major focus of Jaclyn’s current research is understanding host cell death and inflammatory responses to infection with bacterial gastrointestinal pathogens including E. coli, Salmonella, and Shigella. She hopes that her work will provide insights into immune mechanisms that are key for maintaining gut homeostasis in those suffering from inflammatory disorders of the bowel.
Seminar Host: Prof Si Ming Man, Department of Immunology and Infectious Diseases