“Combating Multidrug-Resistant Superbugs by Targeting the Host-Pathogen Interaction”

Abstract:

Antibiotic resistance presents an ever increasing challenge to the public health with a dearth of new drugs in the development pipeline. A single-minded focus on direct antimicrobial activities overlooks the fact that significant infections are really a disease of the host-pathogen interaction. Indeed, before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system.  We see value in exploring potential novel therapeutic approaches for drug-resistant bacteria that aim to tip the host-pathogen interaction back in favor of the host. This talk will illustrate novel therapeutics that mitigate bacterial virulence, re-sensitize the pathogen to innate immune killing or directly boost the antibacterial killing capacity of host cells. Current MIC testing can be misleading, and overlook potent antibiotic activities that are recognized only the context of the normal innate immune system.  In this new discovery and treatment framework, drugs used in medicine for other indications, antibiotics otherwise deemed ineffective, or natural host cell membranes can be “rediscovered” or “repurposed" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) multi-drug Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumonia, and mcr-1+ Escherichia coli.

About Victor Nizet:

Victor Nizet is Distinguished Professor and Vice Chair for Basic Research and Chief of the Division of Host-Microbe Systems & Therapeutics at the University of California, San Diego (UCSD), School of Medicine as well as Distinguished Professor at UCSD Skaggs School of Pharmacy & Pharmaceutical Sciences. Dr. Nizet is a graduate of Reed College, received his medical training at Stanford University School of Medicine, completed a Residency and Chief Residency in Pediatrics at Harvard University's Children's Hospital in Boston, Massachusetts, and a then a Fellowship in Pediatric Infectious Diseases at the University of Washington’s Children's Hospital in Seattle. Dr. Nizet leads a basic and translational research laboratory focused on discovering virulence factors of invasive bacterial pathogens, elucidating mechanisms of host innate immunity, and novel approaches to infectious disease therapy. Dr. Nizet has authored over 525 peer-reviewed publications and has collaborated with several biotechnology interests in developing new antibiotic and immune-based therapies against drug-resistant pathogens.  work has been recognized by the E. Mead Johnson Award for Research in Pediatrics, the DC White Award from the Interdisciplinary Research and Mentoring, and an NIH Merit Award.  He has been elected to the American Society for Clinical Investigation, the Association of American Physicians, the American Academy of Microbiology, the American Association for the Advancement of Science, the American Institute for Medical and Biological Engineering, and the National Academy of Medicine. Details of his research program can be found on the laboratory website: http://nizetlab.ucsd.edu.