Pathogenic bacteria make surgical strikes on host ubiquitin signaling

Key Facts

Speaker: Prof. Jonathan Pruneda
Employer and Department:
Oregon Health & Science University
Location:
MSI-SLT
Date and Time:
Fri 23rd Jun 2023 - 10:00

Abstract:

A healthy immune response to infection requires rapid and robust post-translational ubiquitin signaling following pathogen detection. Unfortunately, pathogenic bacteria have evolved secreted effector proteins that redirect, inhibit, or eliminate host ubiquitin signaling events in order to facilitate invasion, replication, and persistence. We have identified remarkable strategies employed by bacteria to subvert host ubiquitin signaling with surgical precision, providing access to discrete areas of host cell biology. Our recent focus has been a particular type of ubiquitin signal – Lys6-linked poly-ubiquitin – for which signaling roles are poorly understood. Paradoxically, we have found that some pathogens secrete ligases that upregulate Lys6 poly-ubiquitin, while others secrete proteases that specifically remove this signal. I will present our latest work on how pathogens achieve this targeted manipulation of ubiquitin signaling, why it might be to their evolutionary advantage, and what we can learn from these interactions about ubiquitin signaling within the host-pathogen interface.

Bio:

Jonathan Pruneda earned his bachelor’s degrees in Biochemistry and Microbiology from Washington State University in 2008. He subsequently earned his Ph.D. in Biochemistry from the University of Washington in 2012 after performing his thesis work with Dr. Rachel Klevit. His thesis project used biochemical, structural, and biophysical approaches to study the enzymatic transfer of ubiquitin, a post-translational modifier that regulates many aspects of human biology. For his postdoctoral work, he procured an EMBO Long-Term Postdoctoral Fellowship and joined the laboratory of Dr. David Komander at the MRC Laboratory of Molecular Biology. His postdoctoral work focused on how pathogenic bacteria manipulate host ubiquitin signaling responses through the action of secreted deubiquitinating enzymes. This work highlighted an apparent evolutionary pressure that has led to the convergent evolution of ubiquitin-modifying enzymes in pathogenic bacteria, and inspired his current work as Assistant Professor in the Department of Molecular Microbiology & Immunology at Oregon Health & Science University. Since his arrival in late 2018, Dr. Pruneda’s research interests have surrounded the many mechanisms that bacteria have evolved to hijack host ubiquitin signaling, including deubiquitinases that reverse ubiquitin signaling as well as enzymes that write new signals. He was recently awarded an R35 Maximizing Investigators’ Research Award from the NIH to fund his research program, and in honor of his commitment to teaching he was recently awarded an Excellence in Teaching Award from the OHSU School of Medicine.