Department of Microbiology and Molecular Genetics

Leigh Knodler, Ph.D.

Associate Professor

Training & Education

Dr. Knodler received her Ph.D. in Biochemistry and Molecular Genetics from the University of New South Wales, Australia, studying novel metabolic pathways in the protozoan parasite, Giardia lamblia. For postdoctoral research, she first studied developmental gene regulation in Giardia at the University of California, San Diego, then switched her research focus to another foodborne pathogen, Salmonella enterica, at the University of British Columbia, Canada.” Dr. Knodler continued her studies on Salmonella-host cell interactions as a Staff Scientist at the Rocky Mountain Laboratories, NIAID, NIH before starting her own research laboratory at Washington State University in 2012. She received tenure and promotion there in 2019 and joined the Department of Microbiology and Molecular Genetics in 2023.

Research Interests

Salmonella enterica is the leading bacterial cause of food-borne illness in humans in the USA. Host-to-host transmission of this bacterium is via the fecal-oral route, therefore preventing or minimizing fecal shedding is critical for disease control. Once ingested in contaminated food or water, Salmonella lives inside of the cells lining the gut. Our research aims to understand how Salmonella enterica proliferates in these cells and then how it breaks free. Our recent work revealed that Salmonella enterica has distinct intracellular lifestyles in different host cell types. Specifically, after entering gut epithelial cells, a subset of bacteria breakout of their internalization vacuole, then rapidly proliferate in the cell cytosol. This triggers a series of events – initiation of inflammatory signals, epithelial cell lysis, death and sloughing into the gut lumen – which leads to bacterial spread within and between hosts. We are now focused on identifying bacterial and host factors required for this important step in the infectious cycle.  

Confocal microscope image of Salmonella-infected epithelial cells showing heterogeneity in intracellular replication. Bacterial growth in the cytosol (top cell in image) is more prolific than that in a membrane-bound vacuole (bottom three cells). Green = Salmonella, red = lysosomes, blue = nuclei

Featured Publications

Powers TR, Haeberle AL, Predeus AV, Hammarlöf DL, Cundiff JA, Saldaña-Ahuactzi Z, Hokamp K, Hinton JCD, Knodler LA. Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica. PLoS Pathog. 2021 Aug 30;17(8):e1009280. doi: 10.1371/journal.ppat.1009280. PMID: 34460873; PMCID: PMC8432900.

Crowley SM, Han X, Allaire JM, Stahl M, Rauch I, Knodler LA, Vallance BA. Intestinal restriction of Salmonella Typhimurium requires caspase-1 and caspase-11 epithelial intrinsic inflammasomes. PLoS Pathog. 2020 Apr 13;16(4):e1008498. doi: 10.1371/journal.ppat.1008498. PMID: 32282854; PMCID: PMC7179941.

Lau N, Haeberle AL, O'Keeffe BJ, Latomanski EA, Celli J, Newton HJ, Knodler LA. SopF, a phosphoinositide binding effector, promotes the stability of the nascent Salmonella-containing vacuole. PLoS Pathog. 2019 Jul 24;15(7):e1007959. doi: 10.1371/journal.ppat.1007959. PMID: 31339948; PMCID: PMC6682159.

Wrande M, Andrews-Polymenis H, Twedt DJ, Steele-Mortimer O, Porwollik S, McClelland M, Knodler LA. Genetic Determinants of Salmonella enterica Serovar Typhimurium Proliferation in the Cytosol of Epithelial Cells. Infect Immun. 2016 Nov 18;84(12):3517-3526. doi: 10.1128/IAI.00734-16. PMID: 27698022; PMCID: PMC5116728.

Du J, Reeves AZ, Klein JA, Twedt DJ, Knodler LA, Lesser CF. The type III secretion system apparatus determines the intracellular niche of bacterial pathogens. Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4794-9. doi: 10.1073/pnas.1520699113. Epub 2016 Apr 12. PMID: 27078095; PMCID: PMC4855615.

All Knodler publications