Virulence factor regulation in enteric pathogens
Bacterial pathogens must finely tune virulence gene expression to adapt to the changing environments they encounter within a host. Two key signals that shape this response are iron availability and oxidative stress, which vary across tissues and between individuals. The Auerbuch Stone Lab studies how enteric pathogens use the iron-sulfur (Fe-S) cluster coordinating transcription factor IscR to sense these cues and coordinate virulence gene expression. By uncovering how IscR integrates information about iron and oxidative stress to control infection, we aim to understand how the host environment influences infection dynamics.
Yersinia, Salmonella enterica, and Vibrio vulnificus all require IscR to express critical virulence factors such as the type III secretion system (T3SS). The Auerbuch Stone lab uses the food-borne pathogen Yersinia pseudotuberculosis as a model system to study how IscR cooperates with the H-NS global xenogeneic silencer to strategically express the T3SS and other virulence factors in response to changes in the host tissue microenvironment.
T3SS inhibitor drug discovery
With increasing incidence of antibiotic resistance, development of new therapies against bacterial pathogens is essential for global public health. For example, every year over 50,000 healthcare-associated Pseudomonas aeruginosa infections occur in the U.S., >6,000 of which are caused by multidrug resistant strains. The T3SS represents an excellent drug target because it is externally accessible to small molecules and enables virulence of Pseudomonas, Salmonella, Chlamydia, Yersinia, and numerous other important pathogens. We have developed a high throughput screening pipeline to discover T3SS inhibitors. In collaboration with the Lokey, Crews, and MacMillan labs at UC Santa Cruz, the Linington Lab at Simon Fraser University in Canada, and the UCSC Chemical Screening Center, we have identified several new classes of T3SS inhibitors.
Check out Dr. Auerbuch Stone’s short talk on T3SS inhibitor research at the UC Santa Cruz Interdisciplinary Science Symposium from 2023.