Leigh Knodler
University of Vermont, VT·Microbiology & Immunology
Many bacteria that cause diarrhea succeed by forcing their way inside the cells lining the intestine, then surviving there. Up to half of gastroenteritis cases are never traced to a cause, partly because some gut bacteria have barely been studied.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
Providencia alcalifaciens
Salmonella Typhimurium
non-typhoidal Salmonella
- Grants
- 2 known grants, through Jan 2028
What they work on
- Determine whether nine genes in the 40-kilobase type III secretion gene cluster on the Providencia alcalifaciens plasmid drive invasion of host cells, combining computational prediction, in vitro biochemistry and infection of cultured non-phagocytic cells.
- Establish an oral-challenge mouse model to compare gut colonization and host response between invasive and non-invasive P. alcalifaciens isolates, defining how intestinal epithelial invasion contributes to disease by the natural infection route.
- Separate human intestinal epithelial cells harboring cytosolic versus vacuole-enclosed Salmonella Typhimurium using a fluorescent bacterial reporter and cell sorting, then read both bacterial and host gene activity by dual RNA sequencing.
- Apply the same sorting and dual RNA-seq approach to infected macrophages, and use genetic disruption of candidate bacterial and host genes to test which ones determine whether Salmonella sits in the cytosol or a vacuole.
More about the research
Both projects here ask the same underlying question from different angles: which bacterial genes let a gut bacterium invade host cells, and what happens inside the cell once it is there. The work uses cultured human intestinal cells and immune cells, bacterial genetics, genome comparisons and mouse infection models.
Why it matters
Because up to half of gastroenteritis cases go undiagnosed, pinning down whether and how Providencia alcalifaciens causes disease could expand the list of agents clinicians and public health labs consider in diarrheal outbreaks. Mapping which bacterial and host genes dictate where Salmonella hides inside human cells could reveal vulnerabilities to target with drugs that block virulence or enlist the immune system, rather than conventional antibiotics.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Johanna Elfenbein
University of Wisconsin-Madison, WI·Microbiology & Immunology
Test whether the membrane protein gene yeiH is needed for Salmonella Typhimurium to survive during infection, using animal models of colitis and sepsis.
Jorge E Galan
Yale University, CT·Microbiology & Immunology
Determine how short N-terminal secretion signals and dedicated chaperones direct client proteins to the type III secretion injectisome, the syringe-like machine Salmonella uses to inject proteins into host cells.
Shelley Payne
University of Texas at Austin, TX·Microbiology & Immunology
Determine how carbon-source availability tells Shigella flexneri where it is in the host, by testing mutants defective in specific carbon metabolism pathways for invasion, intracellular replication, and cell-to-cell spread in human cells.
The school
University of Vermont: 16 labs on PI Pages, $246M a year on research, 76 research doctorates a year.
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